2021/11/11 更新

写真a

サトウ アヤノ
佐藤 あやの
SATOH Ayano
所属
ヘルスシステム統合科学学域 准教授
職名
准教授
外部リンク

学位

  • 博士(理学) ( お茶の水女子大学 )

研究キーワード

  • biotechnology

  • intracellular trafficking

  • organelle

  • 化学生物学

  • 動物実験代替法

  • オルガネラ

  • バイオテクノロジー

  • 細胞生物学

  • 糖鎖生物学

  • cell biology

  • glycobiology

  • biochemistry

  • 細胞内輸送

  • 生化学 生物工学

研究分野

  • ライフサイエンス / 機能生物化学

  • ナノテク・材料 / 生物分子化学

  • ナノテク・材料 / ナノ材料科学

  • ナノテク・材料 / ナノバイオサイエンス

  • ライフサイエンス / 細胞生物学

経歴

  • 岡山大学 大学院ヘルスシステム統合科学研究科   准教授

    2019年4月 - 現在

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  • 岡山大学   The Graduate School of Natural Science and Technology   准教授

    2011年6月 - 2019年3月

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所属学協会

▼全件表示

委員歴

  • Frontiers in Cell and Developmental Biology   編集委員  

    2021年 - 現在   

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  • Trends in Glycoscience and Glycotechnology   編集委員  

    2017年 - 現在   

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    団体区分:学協会

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  • Cell Biology International   編集委員  

    2016年 - 現在   

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    団体区分:学協会

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  • 日本糖質学会   評議員  

    2009年 - 現在   

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    団体区分:学協会

    日本糖質学会

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論文

  • Glycoprotein Semisynthesis by Chemical Insertion of Glycosyl Asparagine Using a Bifunctional Thioacid-Mediated Strategy. 国際誌

    Kota Nomura, Yuta Maki, Ryo Okamoto, Ayano Satoh, Yasuhiro Kajihara

    Journal of the American Chemical Society   143 ( 27 )   10157 - 10167   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Glycosylation is a major modification of secreted and cell surface proteins, and the resultant glycans show considerable heterogeneity in their structures. To understand the biological processes arising from each glycoform, the preparation of homogeneous glycoproteins is essential for extensive biological experiments. To establish a more robust and rapid synthetic route for the synthesis of homogeneous glycoproteins, we studied several key reactions based on amino thioacids. We found that diacyl disulfide coupling (DDC) formed with glycosyl asparagine thioacid and peptide thioacid yielded glycopeptides. This efficient coupling reaction enabled us to develop a new glycoprotein synthesis method, such as the bifunctional thioacid-mediated strategy, which can couple two peptides with the N- and C-termini of glycosyl asparagine thioacid. Previous glycoprotein synthesis methods required valuable glycosyl asparagine in the early stage and subsequent multiple glycoprotein synthesis routes, whereas the developed concept can generate glycoproteins within a few steps from peptide and glycosyl asparagine thioacid. Herein, we report the characterization of the DDC of amino thioacids and the efficient ability of glycosyl asparagine thioacid to be used for robust glycoprotein semisynthesis.

    DOI: 10.1021/jacs.1c02601

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  • High-throughput screening of bioactive compounds via new catalytic reaction in the pooled mixture. 国際誌

    Ayano Satoh, Yuta Nishina

    Bioorganic & medicinal chemistry letters   29 ( 19 )   126539 - 126539   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To increase the chances of finding new candidate molecules with medicinal properties, while expending less resource and effort, the present study used pooled substrates as starting materials. A bisindole compound that showed inhibitory activity was then isolated from the mixture, and the activity was improved by optimizing the substituents on the indole skeleton.

    DOI: 10.1016/j.bmcl.2019.06.061

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  • The Golgin Protein Giantin Regulates Interconnections Between Golgi Stacks. 国際誌

    Ayano Satoh, Mitsuko Hayashi-Nishino, Takuto Shakuno, Junko Masuda, Mayuko Koreishi, Runa Murakami, Yoshimasa Nakamura, Toshiyuki Nakamura, Naomi Abe-Kanoh, Yasuko Honjo, Joerg Malsam, Sidney Yu, Kunihiko Nishino

    Frontiers in cell and developmental biology   7   160 - 160   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Golgins are a family of Golgi-localized long coiled-coil proteins. The major golgin function is thought to be the tethering of vesicles, membranes, and cytoskeletal elements to the Golgi. We previously showed that knockdown of one of the longest golgins, Giantin, altered the glycosylation patterns of cell surfaces and the kinetics of cargo transport, suggesting that Giantin maintains correct glycosylation through slowing down transport within the Golgi. Giantin knockdown also altered the sizes and numbers of mini Golgi stacks generated by microtubule de-polymerization, suggesting that it maintains the independence of individual Golgi stacks. Therefore, it is presumed that Golgi stacks lose their independence following Giantin knockdown, allowing easier and possibly increased transport among stacks and abnormal glycosylation. To gain structural insights into the independence of Golgi stacks, we herein performed electron tomography and 3D modeling of Golgi stacks in Giantin knockdown cells. Compared with control cells, Giantin-knockdown cells had fewer and smaller fenestrae within each cisterna. This was supported by data showing that the diffusion rate of Golgi membrane proteins is faster in Giantin-knockdown Golgi, indicating that Giantin knockdown structurally and functionally increases connectivity among Golgi cisternae and stacks. This increased connectivity suggests that contrary to the cis-golgin tether model, Giantin instead inhibits the tether and fusion of nearby Golgi cisternae and stacks, resulting in transport difficulties between stacks that may enable the correct glycosylation of proteins and lipids passing through the Golgi.

    DOI: 10.3389/fcell.2019.00160

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  • Do the Golgi Glycosylation Enzymes Cycle between the Endoplasmic Reticulum and the Golgi Apparatus? 査読

    Satoh, Ayano, Honjo, Yasuko

    Trends in Glycoscience and Glycotechnology   29 ( 167 )   E49 - E50   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Gakushin Publishing Company  

    DOI: 10.4052/tigg.1708.6E

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  • Enhanced cellular engraftment of adipose-derived mesenchymal stem cell spheroids by using nanosheets as scaffolds. 国際誌

    Hisato Nagano, Yoshitaka Suematsu, Megumi Takuma, Shimpo Aoki, Ayano Satoh, Eiji Takayama, Manabu Kinoshita, Yuji Morimoto, Shinji Takeoka, Toshinori Fujie, Tomoharu Kiyosawa

    Scientific reports   11 ( 1 )   14500 - 14500   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The short survival time of transplanted adipose-derived mesenchymal stem cells (ASCs) is a problem for skin wound healing. Transplantation after the formation of cellular spheroids has been investigated as a promising method for prolonging cellular survival. However, there have been technical restrictions for transplantation of spheroids in clinical practice. Here, we show an effective method for transplantation of ASC spheroids onto skin wounds in order to efficiently cure refractory ulcers. To assist anchoring of spheroids onto skin wounds, we used a 120-nm-thick free-standing film (nanosheet) that has a highly adhesive property. Bioluminescence imaging showed that ASC spheroids carried by the nanosheet survived for 14 days, which is about two-times longer than that previously reported. Wounds treated with a nanosheet carrying ASC spheroids were 4-times smaller than untreated wounds on day 14. This method for transplantation of spheroids could be applied to cell therapy for various refractory skin wounds.

    DOI: 10.1038/s41598-021-93642-6

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  • Horseradish peroxidase interacts with the cell wall peptidoglycans on oral bacteria. 国際誌

    Hirofumi Mizuno, Eiji Takayama, Ayano Satoh, Takeshi Into, Masanori Adachi, Daisuke Ekuni, Koji Yashiro, Masako Mizuno-Kamiya, Motohiko Nagayama, Seitaro Saku, Takaaki Tomofuji, Yutaka Doi, Yukitaka Murakami, Nobuo Kondoh, Manabu Morita

    Experimental and therapeutic medicine   20 ( 3 )   2822 - 2827   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Salivary peroxidase and myeloperoxidase are known to display antibacterial activity against oral microbes, and previous indications have pointed to the possibility that horseradish peroxidase (HRP) adsorbs onto the membrane of the major oral streptococci, Streptococcus mutans and Streptococcus sanguinis (S. sanguinis). However, the mechanism of interaction between HRP and the bacterial cell wall component is unclear. Dental plaques containing salivary glycoproteins and extracellular microbial products are visualized with 'dental plaque disclosing agent', and are controlled within dental therapy. However, current 'dental plaque disclosing agents' are difficult to evaluate with just dental plaques, since they stain and disclose not only dental plaques but also pellicle formed with salivary glycoproteins on a tooth surface. In this present study, we have demonstrated that HRP interacted with the cell wall component of the major gram-positive bacterial peptidoglycan, but not the major cell wall component of gram-negative bacteria lipopolysaccharide. Furthermore, we observed that the adsorbed HRP labeled with fluorescence was detected on the major oral gram-positive strains S. sanguinis and Streptococcus salivarius (S. salivarius), but not on a gram-negative strain, Escherichia coli (E. coli). Furthermore, we have demonstrated that the combination of HRP and chromogenic substrate clearly disclosed the dental plaques and the biofilm developed by S. sanguinis, S. salivarius and the major gram-postive bacteria Lactobacillus casei on tooth surfaces, and slightly disclosed the biofilm by E. coli. The combination of HRP and chromogenic substrate did not stain either the dental pellicle with the salivary glycoprotein mucin, or naked tooth surfaces. These results have suggested the possibility that the adsorption activity of HRP not only contributes to the evaluation of dental plaque, but that enzymatic activity of HRP may also contribute to improve dental hygiene.

    DOI: 10.3892/etm.2020.9016

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  • Highly reliable, targeted photothermal cancer therapy combined with thermal dosimetry using a near-infrared absorbent. 国際誌

    Shinsuke Nomura, Yuji Morimoto, Hironori Tsujimoto, Masashi Arake, Manabu Harada, Daizoh Saitoh, Isao Hara, Eiichi Ozeki, Ayano Satoh, Eiji Takayama, Kazuo Hase, Yoji Kishi, Hideki Ueno

    Scientific reports   10 ( 1 )   9765 - 9765   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Photothermal therapy (PTT) using a photo-absorbent in the near-infrared (NIR) region is an effective methodology for local cancer treatment. Before PTT using a NIR absorbent is executed, the operator generally determines the two parameters of fluence rate and irradiation time. However, even if the irradiation parameters are unchanged, the therapeutic effect of PTT is often different for individual tumors. Hence, we examined the therapeutic effect of PTT using a NIR absorbent (ICG lactosome) while changing two parameters (fluence rate and irradiation time) in various combinations. As a result, there was no robust correlation between those parameters and the therapeutic effect. Compared to those parameters, we found that a more reliable determinant was maintenance of the tumor temperature above 43 °C during NIR irradiation. To reconfirm the significance of the determinant, we developed a new system that can regulate the temperature at the NIR irradiation site at a constant level. By using the new system, we verified the treatment outcomes for tumors in which the NIR absorbent had accumulated. All of the tumors that had been kept at 43 °C during NIR irradiation were cured, while none of the tumors that had been kept at a temperature below 41 °C were cured. In conclusion, PTT using a NIR absorbent with thermal dosimetry is a highly reliable treatment for cancer.

    DOI: 10.1038/s41598-020-66646-x

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  • Knockout of MMP3 Weakens Solid Tumor Organoids and Cancer Extracellular Vesicles 国際誌

    Eman A. Taha, Chiharu Sogawa, Yuka Okusha, Hotaka Kawai, May Wathone Oo, Abdellatif Elseoudi, Yanyin Lu, Hitoshi Nagatsuka, Satoshi Kubota, Ayano SATOH, Kuniaki Okamoto, Takanori Eguchi

    Cancers   12 ( 5 )   1260 - 1260   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:{MDPI} {AG}  

    The tumor organoid (tumoroid) model in three-dimensional (3D) culture systems has been developed to reflect more closely the in vivo tumors than 2D-cultured tumor cells. Notably, extracellular vesicles (EVs) are efficiently collectible from the culture supernatant of gel-free tumoroids. Matrix metalloproteinase (MMP) 3 is a multi-functional factor playing crucial roles in tumor progression. However, roles of MMP3 within tumor growth and EVs have not unveiled. Here, we investigated the protumorigenic roles of MMP3 on integrities of tumoroids and EVs. We generated MMP3-knockout (KO) cells using the CRISPR/Cas9 system from rapidly metastatic LuM1 tumor cells. Moreover, we established fluorescent cell lines with palmitoylation signal-fused fluorescent proteins (tdTomato and enhanced GFP). Then we confirmed the exchange of EVs between cellular populations and tumoroids. LuM1-tumoroids released large EVs (200-1000 nm) and small EVs (50-200 nm) while the knockout of MMP3 resulted in the additional release of broken EVs from tumoroids. The loss of MMP3 led to a significant reduction in tumoroid size and the development of the necrotic area within tumoroids. MMP3 and CD9 (a category-1 EV marker tetraspanin protein) were significantly down-regulated in MMP3-KO cells and their EV fraction. Moreover, CD63, another member of the tetraspanin family, was significantly reduced only in the EVs fractions of the MMP3-KO cells compared to their counterpart. These weakened phenotypes of MMP3-KO were markedly rescued by the addition of MMP3-rich EVs or conditioned medium (CM) collected from LuM1-tumoroids, which caused a dramatic rise in the expression of MMP3, CD9, and Ki-67 (a marker of proliferating cells) in the MMP3-null/CD9-low tumoroids. Notably, MMP3 enriched in tumoroids-derived EVs and CM deeply penetrated recipient MMP3-KO tumoroids, resulting in a remarkable enlargement of solid tumoroids, while MMP3-null EVs did not. These data demonstrate that EVs can mediate molecular transfer of MMP3, resulting in increasing the proliferation and tumorigenesis, indicating crucial roles of MMP3 in tumor progression.

    DOI: 10.3390/cancers12051260

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  • Development of an experimental method of systematically estimating protein expression limits in HEK293 cells. 国際誌

    Yoshihiro Mori, Yuki Yoshida, Ayano Satoh, Hisao Moriya

    Scientific reports   10 ( 1 )   4798 - 4798   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Protein overexpression sometimes causes cellular defects, although the underlying mechanism is still unknown. A protein's expression limit, which triggers cellular defects, is a useful indication of the underlying mechanism. In this study, we developed an experimental method of estimating the expression limits of target proteins in the human embryonic kidney cell line HEK293 by measuring the proteins' expression levels in cells that survived after the high-copy introduction of plasmid DNA by which the proteins were expressed under a strong cytomegalovirus promoter. The expression limits of nonfluorescent target proteins were indirectly estimated by measuring the levels of green fluorescent protein (GFP) connected to the target proteins with the self-cleaving sequence P2A. The expression limit of a model GFP was ~5.0% of the total protein, and sustained GFP overexpression caused cell death. The expression limits of GFPs with mitochondria-targeting signals and endoplasmic reticulum localization signals were 1.6% and 0.38%, respectively. The expression limits of four proteins involved in vesicular trafficking were far lower compared to a red fluorescent protein. The protein expression limit estimation method developed will be valuable for defining toxic proteins and consequences of protein overexpression.

    DOI: 10.1038/s41598-020-61646-3

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  • Synthesis and characterization of conductive flexible cellulose carbon nanohorn sheets for human tissue applications. 国際誌

    Karthik Paneer Selvam, Taichi Nagahata, Kosuke Kato, Mayuko Koreishi, Toshiyuki Nakamura, Yoshimasa Nakamura, Takeshi Nishikawa, Ayano Satoh, Yasuhiko Hayashi

    Biomaterials research   24   18 - 18   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Conductive sheets of cellulose and carbon nanomaterials and its human skin applications are an interesting research aspect as they have potential for applications for skin compatibility. Hence it is needed to explore the effects and shed light on these applications. Method: To fabricate wearable, portable, flexible, lightweight, inexpensive, and biocompatible composite materials, carbon nanohorns (CNHs) and hydroxyethylcellulose (HEC) were used as precursors to prepare CNH-HEC (Cnh-cel) composite sheets. Cnh-cel sheets were prepared with different loading concentrations of CNHs (10, 20 50,100 mg) in 200 mg cellulose. To fabricate the bio-compatible sheets, a pristine composite of CNHs and HEC was prepared without any pretreatment of the materials. Results: The obtained sheets possess a conductivity of 1.83 × 10- 10 S/m and bio-compatible with human skin. Analysis for skin-compatibility was performed for Cnh-cel sheets by h-CLAT in vitro skin sensitization tests to evaluate the activation of THP-1 cells. It was found that THP-1 cells were not activated by Cnh-cel; hence Cnh-cel is a safe biomaterial for human skin. It was also found that the composite allowed only a maximum loading of 100 mg to retain the consistent geometry of free-standing sheets of < 100 μm thickness. Since CNHs have a unique arrangement of aggregates (dahlia structure), the composite is homogeneous, as verified by transmission electron microscopy (TEM) and, scanning electron microscopy (SEM), and other functional properties investigated by Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), conductivity measurement, tensile strength measurement, and skin sensitization. Conclusion: It can be concluded that cellulose and CNHs sheets are conductive and compatible to human skin applications.

    DOI: 10.1186/s40824-020-00194-3

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  • Hematopoietic Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells 査読 国際誌

    Ghmkin Hassan, SAID M AFIFY, Neha Nair, Kazuki Kumon, Amira Osman, Juan Du, Hager Mansour, Hagar A Abu Quora, Hend M Nawara, Ayano SATOH, Maram H. Zahra, Nobuhiro Okada, Akimasa Seno, Masaharu Seno

    Cancers   12 ( 1 )   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cancer stem cells (CSCs) represent the subpopulation of cancer cells with the ability to differentiate into other cell phenotypes and initiated tumorigenesis. Previously, we reported generating CSCs from mouse induced pluripotent stem cells (miPSCs). Here, we investigated the ability of the CSCs to differentiate into hematopoietic cells. First, the primary cells were isolated from malignant tumors that were formed by the CSCs. Non-adherent cells (NACs) that arose from adherent cells were collected and their viability, as well as the morphology and expression of hematopoietic cell markers, were analyzed. Moreover, NACs were injected into the tail vein of busulfan conditioned Balb/c nude mice. Finally, CSCs were induced to differentiate to macrophages while using IL3 and SCF. The round nucleated NACs were found to be viable, positive for hematopoietic lineage markers and CD34, and expressed hematopoietic markers, just like homing to the bone marrow. When NACs were injected into mice, Wright-Giemsa staining showed that the number of white blood cells got higher than those in the control mice after four weeks. CSCs also showed the ability to differentiate toward macrophages. CSCs were demonstrated to have the potential to provide progenies with hematopoietic markers, morphology, and homing ability to the bone marrow, which could give new insight into the tumor microenvironment according to the plasticity of CSCs.

    DOI: 10.3390/cancers12010082

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  • Yeast screening system reveals the inhibitory mechanism of cancer cell proliferation by benzyl isothiocyanate through down-regulation of Mis12. 国際誌

    Naomi Abe-Kanoh, Narumi Kunisue, Takumi Myojin, Ayako Chino, Shintaro Munemasa, Yoshiyuki Murata, Ayano Satoh, Hisao Moriya, Yoshimasa Nakamura

    Scientific reports   9 ( 1 )   8866 - 8866   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Benzyl isothiocyanate (BITC) is a naturally-occurring isothiocyanate derived from cruciferous vegetables. BITC has been reported to inhibit the proliferation of various cancer cells, which is believed to be important for the inhibition of tumorigenesis. However, the detailed mechanisms of action remain unclear. In this study, we employed a budding yeast Saccharomyces cerevisiae as a model organism for screening. Twelve genes including MTW1 were identified as the overexpression suppressors for the antiproliferative effect of BITC using the genome-wide multi-copy plasmid collection for S. cerevisiae. Overexpression of the kinetochore protein Mtw1 counteracts the antiproliferative effect of BITC in yeast. The inhibitory effect of BITC on the proliferation of human colon cancer HCT-116 cells was consistently suppressed by the overexpression of Mis12, a human orthologue of Mtw1, and enhanced by the knockdown of Mis12. We also found that BITC increased the phosphorylated and ubiquitinated Mis12 level with consequent reduction of Mis12, suggesting that BITC degrades Mis12 through an ubiquitin-proteasome system. Furthermore, cell cycle analysis showed that the change in the Mis12 level affected the cell cycle distribution and the sensitivity to the BITC-induced apoptosis. These results provide evidence that BITC suppresses cell proliferation through the post-transcriptional regulation of the kinetochore protein Mis12.

    DOI: 10.1038/s41598-019-45248-2

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  • Highly reliable, targeted photothermal cancer therapy combined with thermal dosimetry using indocyanine green lactosome 査読 国際誌

    Shinsuke Nomura, Yuji Morimoto, Hironori Tsujimoto, Manabu Harada, Daizoh Saitoh, Isao Hara, Eiichi Ozeki, Ayano Satoh, Eiji Takayama, Kazuo Hase, Yoji Kishi, Hideki Ueno

    2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cold Spring Harbor Laboratory  

    DOI: 10.1101/659334

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  • Suppression effect on IFN-γ of adipose tissue-derived mesenchymal stem cells isolated from β2-microglobulin-deficient mice. 国際誌

    Junko Masuda, Eiji Takayama, Tatsuo Ichinohe, Warren Strober, Masako Mizuno-Kamiya, Tomokatsu Ikawa, Atsushi Kitani, Harumi Kawaki, Ivan Fuss, Hiroshi Kawamoto, Akimasa Seno, Arun Vaidyanath, Naoki Umemura, Akifumi Mizutani, Tomonari Kasai, Yasuko Honjo, Ayano Satoh, Hiroshi Murakami, Yoshimoto Katsura, Nobuo Kondoh, Masaharu Seno

    Experimental and therapeutic medicine   16 ( 5 )   4277 - 4282   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Administration of bone marrow-derived mesenchymal stem cells (MSCs) is a possible treatment for graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation and other inflammatory conditions. To address the mechanism of immunosuppression by MSCs, in particular those derived from adipose tissue (AMSCs), AMSCs were isolated from three different mouse strains, and the suppressive capacity of the AMSCs thus obtained to suppress interferon (IFN)-γ generation in mixed lymphocyte reaction cultures serving as an in vitro model of GVHD were assessed. It was revealed that the AMSCs had a potent capacity to suppress IFN-γ production regardless of their strain of origin and that such suppression was not associated with production of interleukin-10. In addition, the results demonstrated that β2-microglobulin (β2m)-deficient AMSCs from β2m-/- mice were also potent suppressor cells, verifying the fact that the mechanism underlying the suppression by AMSCs is independent of major histocompatibility complex (MHC) class I expression or MHC compatibility. As AMSCs appear to have immunosuppressive properties, AMSCs may be a useful source of biological suppressor cells for the control of GVHD in humans.

    DOI: 10.3892/etm.2018.6689

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  • Cytokine Expression and Macrophage Localization in Xenograft and Allograft Tumor Models Stimulated with Lipopolysaccharide. 国際誌

    Junko Masuda, Tsukasa Shigehiro, Takuma Matsumoto, Ayano Satoh, Akifumi Mizutani, Chiho Umemura, Shoki Saito, Mayumi Kijihira, Eiji Takayama, Akimasa Seno, Hiroshi Murakami, Masaharu Seno

    International journal of molecular sciences   19 ( 4 )   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    T cell-deficient mice such as nude mice are often used to generate tumor xenograft for the development of anticancer agents. However, the functionality of the other immune cells including macrophages, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs) in the xenograft are largely unknown. Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with MDSCs in tumor microenvironments regulates cancer progression. Nude mice are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The tumor microenvironment in a xenograft, comprising human and mouse cells, exhibits more complex bidirectional signaling and function than that of allograft. Here, we evaluated the differences of myeloid cells between them. Plasma interferon-&gamma; and interleukin-18 concentrations in the xenograft tumor model after lipopolysaccharide (LPS) administration were significantly higher than those in the allograft tumor model. MHC class I, II, and CD80 expression levels were increased in CD11b⁺ and MDSC populations after LPS administration in the spleen of a xenograft tumor model but not in that of an allograft tumor model. Additionally, the number of CD80- and mannose receptor C type 1 (MRC1)-expressing cells was decreased upon LPS administration in the tumor of the xenograft tumor. These results suggest that functions of macrophages and DCs are sustained in the xenograft, whereas their functions in response to LPS were suppressed in the allograft. The findings will encourage the consideration of the effects of myeloid cells in the xenograft for drug development.

    DOI: 10.3390/ijms19041261

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  • Correction: A RasGAP, DAB2IP, regulates lipid droplet homeostasis by serving as GAP toward RAB40C. 国際誌

    Xiaomin Luo, Chunman Li, Ran Tan, Xiaohui Xu, William K K Wu, Ayano Satoh, Tuanlao Wang, Sidney Yu

    Oncotarget   9 ( 17 )   14035 - 14035   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    [This corrects the article DOI: 10.18632/oncotarget.19960.].

    DOI: 10.18632/oncotarget.24600

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  • COPI-TRAPPII activates Rab18 and regulates its lipid droplet association 査読 国際誌

    Chunman Li, Xiaomin Luo, Shan Zhao, Gavin K. Y. Siu, Yongheng Liang, Hsiao Chang Chan, Ayano Satoh, Sidney S. B. Yu

    EMBO JOURNAL   36 ( 4 )   441 - 457   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    The transport protein particle (TRAPP) was initially identified as a vesicle tethering factor in yeast and as a guanine nucleotide exchange factor (GEF) for Ypt1/Rab1. In mammals, structures and functions of various TRAPP complexes are beginning to be understood. We found that mammalian TRAPPII was a GEF for both Rab18 and Rab1. Inactivation of TRAPPII-specific subunits by various methods including siRNA depletion and CRISPR-Cas9-mediated deletion reduced lipolysis and resulted in aberrantly large lipid droplets. Recruitment of Rab18 onto lipid droplet (LD) surface was defective in TRAPPII-deleted cells, but the localization of Rab1 on Golgi was not affected. COPI regulates LD homeostasis. We found that the previously documented interaction between TRAPPII and COPI was also required for the recruitment of Rab18 to the LD. We hypothesize that the interaction between COPI and TRAPPII helps bring TRAPPII onto LD surface, and TRAPPII, in turn, activates Rab18 and recruits it on the LD surface to facilitate its functions in LD homeostasis.

    DOI: 10.15252/embj.201694866

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  • A RasGAP, DAB2IP, regulates lipid droplet homeostasis by serving as GAP toward RAB40C 査読 国際誌

    Luo, Xiaomin, Li, Chunman, Tan, Ran, Xu, Xiaohui, Wu, William K. K., Satoh, Ayano, Wang, Tuanlao, Yu, Sidney

    Oncotarget   8 ( 49 )   85415 - 85427   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IMPACT JOURNALS LLC  

    Lipid droplet (LD) homeostasis involves activities of various RAB small GTPases. Recently, we found RAB40C was one of the RAB proteins regulating LD homeostasis. RAB40C contains a unique SOCS domain that is required for clustering of LDs. However, its precise functional role in LD homeostasis and mechanism of regulation remain largely unknown. In this study, we observed over-accumulation of LDs in cells with RAB40C deleted by Crispr-Cas9 editing. RAB40C appeared to reduce LD accumulation after long term incubation of cells with oleic acid (24 hours). Unexpectedly, we found that Ras GTPase activating protein (GAP), DAB2IP, bound to RAB40C mainly via its GAP domain and could serve as RAB40C GAP. Studies involving overexpression of DAB2IP and its GAP defective mutant and siRNA depletion of DAB2IP all confirmed that DAB2IP negatively regulated the effect of RAB40C on LD homeostasis. These results provide a novel perspective on the regulation of RAB40C and implicate various signalling pathways regulated by DAB2IP, which may play a role in LD homeostasis via RAB40C.

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  • An endoplasmic reticulum protein, Nogo-B, facilitates alcoholic liver disease through regulation of kupffer cell polarization 査読 国際誌

    Park, J. K., Shao, M., Kim, M. Y., Baik, S. K., Cho, M. Y., Utsumi, T., Satoh, A., Ouyang, X., Chung, C., Iwakiri, Y.

    Hepatology   65 ( 5 )   1720 - 1734   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Nogo-B (Reticulon 4B) is an endoplasmic reticulum (ER) resident protein that regulates ER structure and function. Because ER stress is known to induce M2 macrophage polarization, we examined whether Nogo-B regulates M1/M2 polarization of Kupffer cells and alters the pathogenesis of alcoholic liver disease (ALD). M1 and M2 phenotypes were assessed in relation to Nogo-B expression and disease severity in liver specimens from ALD patients (NCT01875211). Liver specimens from wild-type (WT) and Nogo-B knockout (KO) mice fed a control or Lieber-DeCarli ethanol liquid diet (5% ethanol) for 6 weeks were analyzed for liver injury and steatosis. Kupffer cells isolated from WT and Nogo-B KO mice were assessed for M1 and M2 activation. A significant positive correlation was observed between Nogo-B positive Kupffer cells and disease severity in ALD patients (n = 30, r = 0.66, P = 0.048). Furthermore, Nogo-B-positive Kupffer cells were correlated with M1 activation (inducible nitric oxide synthase) (r = 0.50, P = 0.05) and negatively with markers of M2 status (CD163) (r = 20.48, P = 0.07) in these patients. WT mice exhibited significantly increased liver injury (P &lt; 0.05) and higher hepatic triglyceride levels (P &lt; 0.01) compared with Nogo-B KO mice in response to chronic ethanol feeding. Nogo-B in Kupffer cells promoted M1 polarization, whereas absence of Nogo-B increased ER stress and M2 polarization in Kupffer cells. Conclusion: Nogo-B is permissive of M1 polarization of Kupffer cells, thereby accentuating liver injury in ALD in humans and mice. Nogo-B in Kupffer cells may represent a new therapeutic target for ALD.

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  • ULK1 phosphorylates Sec23A and mediates autophagy-induced inhibition of ER-to-Golgi traffic 査読 国際誌

    Gan, W., Zhang, C., Siu, K. Y., Satoh, A., Tanner, J. A., Yu, S.

    BMC Cell Biol   18 ( 1 )   22 - 22   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Autophagy is an inducible autodigestive process that allows cells to recycle proteins and other materials for survival during stress and nutrient deprived conditions. The kinase ULK1 is required to activate this process. ULK1 phosphorylates a number of target proteins and regulates many cellular processes including the early secretory pathway. Recently, ULK1 has been demonstrated to phosphorylate Sec16 and affects the transport of serotonin transporter at the ER exit sites (ERES), but whether ULK1 may affect the transport of other cargo proteins and general secretion has not been fully addressed.
    Results: In this study, we identified Sec23A, a component of the COPII vesicle coat, as a target of ULK1 phosphorylation. Elevated autophagy, induced by amino acid starvation, rapamycin, or overexpression of ULK1 caused aggregation of the ERES, a region of the ER dedicated for the budding of COPII vesicles. Transport of cargo proteins was also inhibited under these conditions and was retained at the ERES. ULK1 phosphorylation of Sec23A reduced the interaction between Sec23A and Sec31A. We identified serine 207, serine 312 and threonine 405 on Sec23A as ULK1 phosphorylation sites. Among these residues, serine 207, when changed to phospho-deficient and phospho-mimicking mutants, most faithfully recapitulated the above-mentioned effects of ULK1 phospho-regulation.
    Conclusion: These findings identify Sec23A as a new target of ULK1 and uncover a mechanism of coordinating intracellular protein transport and autophagy.

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  • Tumor growth limited to subcutaneous site vs tumor growth in pulmonary site exhibit differential effects on systemic immunities 査読 国際誌

    Masuda, J., Takayama, E., Strober, W., Satoh, A., Morimoto, Y., Honjo, Y., Ichinohe, T., Tokuno, S. I., Ishizuka, T., Nakata, T., Mizutani, A., Umemura, N., Kitani, A., Fuss, I. J., Shigehiro, T., Kawaki, H., Mizuno-Kamiya, M., Kondoh, N., Seno, M.

    Oncol Rep   38 ( 1 )   449 - 455   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    To evaluate systemic immunity associated with tumor growth limited to a subcutaneous site versus growth proceeding at multiple tumor sites, we established syngeneic mouse subcutaneous and pulmonary tumor models by local subcutaneous and intravenous injection of colon carcinoma CT26 cells. We found that splenic myeloid-derived suppressor cell (MDSC) levels were significantly increased in the subcutaneous tumor model but not in the pulmonary tumor model. Furthermore, both CD4(+) and CD8(+) T cells as well as CD4(+) Foxp3(+) T cells were significantly decreased in the subcutaneous tumor model and were largely unchanged in the pulmonary tumor model. In addition, the subcutaneous model, but not the pulmonary model, displayed a Thl polarization bias. This bias was characterized by decreased IL-4, IL-9, and IL-10 production, whereas the pulmonary model displayed increased production of IL-W. These results suggest that the mode of tumor development has differential effects on systemic immunity that may, in turn, influence approaches to treatment of cancer patients.

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  • Practical Liposomal Formulation for Taxanes with Polyethoxylated Castor Oil and Ethanol with Complete Encapsulation Efficiency and High Loading Efficiency 査読 国際誌

    Shigehiro, Tsukasa, Masuda, Junko, Saito, Shoki, Khayrani, Apriliana C., Jinno, Kazumasa, Seno, Akimasa, Vaidyanath, Arun, Mizutani, Akifumi, Kasai, Tomonari, Murakami, Hiroshi, Satoh, Ayano, Ito, Tetsuya, Hamada, Hiroki, Seno, Yuhki, Mandai, Tadakatsu, Seno, Masaharu

    Nanomaterials   7 ( 10 )   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Taxanes including paclitaxel and docetaxel are effective anticancer agents preferably sufficient for liposomal drug delivery. However, the encapsulation of these drugs with effective amounts into conventional liposomes is difficult due to their high hydrophobicity. Therefore, an effective encapsulation strategy for liposomal taxanes has been eagerly anticipated. In this study, the mixture of polyethoxylated castor oil (Cremophor EL) and ethanol containing phosphate buffered saline termed as CEP was employed as a solvent of the inner hydrophilic core of liposomes where taxanes should be incorporated. Docetaxel-, paclitaxel-, or 7-oxacetylglycosylated paclitaxel-encapsulating liposomes were successfully prepared with almost 100% of encapsulation efficiency and 29.9, 15.4, or 29.1 mol% of loading efficiency, respectively. We then applied the docetaxel-encapsulating liposomes for targeted drug delivery. Docetaxel-encapsulating liposomes were successfully developed HER2-targeted drug delivery by coupling HER2-specific binding peptide on liposome surface. The HER2-targeting liposomes exhibited HER2-specific internalization and enhanced anticancer activity in vitro. Therefore, we propose the sophisticated preparation of liposomal taxanes using CEP as a promising formulation for effective cancer therapies.

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  • Transient Tcf3 Gene Repression by TALE-Transcription Factor Targeting 査読 国際誌

    Junko Masuda, Hiroshi Kawamoto, Warren Strober, Eiji Takayama, Akifumi Mizutani, Hiroshi Murakami, Tomokatsu Ikawa, Atsushi Kitani, Narumi Maeno, Tsukasa Shigehiro, Ayano Satoh, Akimasa Seno, Vaidyanath Arun, Tomonari Kasai, Ivan J. Fuss, Yoshimoto Katsura, Masaharu Seno

    APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY   180 ( 8 )   1559 - 1573   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HUMANA PRESS INC  

    Transplantation of hematopoietic stem and progenitor cells (HSCs) i.e., self-renewing cells that retain multipotentiality, is now a widely performed therapy for many hematopoietic diseases. However, these cells are present in low number and are subject to replicative senescence after extraction; thus, the acquisition of sufficient numbers of cells for transplantation requires donors able to provide repetitive blood samples and/or methods of expanding cell numbers without disturbing cell multipotentiality. Previous studies have shown that HSCs maintain their multipotentiality and self-renewal activity if TCF3 transcription function is blocked under B cell differentiating conditions. Taking advantage of this finding to devise a new approach to HSC expansion in vitro, we constructed an episomal expression vector that specifically targets and transiently represses the TCF3 gene. This consisted of a vector encoding a transcription activator-like effector (TALE) fused to a Kruppel-associated box (KRAB) repressor. We showed that this TALE-KRAB vector repressed expression of an exogenous reporter gene in HEK293 and COS-7 cell lines and, more importantly, efficiently repressed endogenous TCF3 in a human B lymphoma cell line. These findings suggest that this vector can be used to maintain multipotentiality in HSC being subjected to a long-term expansion regimen prior to transplantation.

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  • Cellular distribution of injected PLGA-nanoparticles in the liver 査読 国際誌

    Jin-Kyu Park, Teruo Utsumi, Young-Eun Seo, Yang Deng, Ayano Satoh, William Mark Saltzman, Yasuko Iwakiri

    NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE   12 ( 5 )   1365 - 1374   2016年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    The cellular fate of nanoparticles in the liver is not fully understood. Because the effectiveness and safety of nanoparticles in liver therapy depends on targeting nanoparticles to the right cell populations, this study aimed to determine a relative distribution of PLGA-nanoparticles (sizes 271 +/- 1.4 nm) among liver cells in vivo. We found that Kupffer cells were the major cells that took up nanoparticles, followed by liver sinusoidal endothelial cells and hepatic stellate cells. Nanoparticles were found in only 7% of hepatocytes. Depletion of Kupffer cells by clodronate liposomes increased nanoparticle retention in liver sinusoidal endothelial cells and hepatic stellate cells, but not in hepatocytes. It is importantly suggested that studies of drug-loaded nanoparticle delivery to the liver have to demonstrate not only uptake of nanoparticles by the target cell type but also non-uptake by other cell types to assess their effect as well as ensure their safety. (C) 2016 Elsevier Inc. All rights reserved.

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  • Transport within the Golgi: For the Study of Glycoprotein Movement 2 査読

    Ayano Satoh, Yasuko Honjo

    TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY   28 ( 161 )   E61 - E62   2016年5月

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    記述言語:英語   出版者・発行元:GAKUSHIN PUBL CO  

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  • S-nitrosylation of Laforin inhibits its phosphatase activity and is implicated in Lafora disease. 査読

    A. Satoh, R. Toyota, R. Imajo, Y. Honjo

    MOLECULAR BIOLOGY OF THE CELL   27   2016年

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    記述言語:英語   出版者・発行元:AMER SOC CELL BIOLOGY  

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    その他リンク: http://orcid.org/0000-0003-3736-1283

  • Pancreatic α-Amylase Controls Glucose Assimilation by Duodenal Retrieval through N-Glycan-specific Binding, Endocytosis, and Degradation 査読 国際誌

    Date K, Satoh A, Iida K, Ogawa H

    J Biol Chem   290 ( 28 )   17439 - 17450   2015年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Comparative Analysis of Cartilage Marker Gene Expression Patterns during Axolotl and Xenopus Limb Regeneration 査読 国際誌

    Kazumasa Mitogawa, Aki Makanae, Ayano Satoh, Akira Satoh

    PLOS ONE   10 ( 7 )   e0133375   2015年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Axolotls (Ambystoma mexicanum) can completely regenerate lost limbs, whereas Xenopus laevis frogs cannot. During limb regeneration, a blastema is first formed at the amputation plane. It is thought that this regeneration blastema forms a limb by mechanisms similar to those of a developing embryonic limb bud. Furthermore, Xenopus laevis frogs can form a blastema after amputation; however, the blastema results in a terminal cone-shaped cartilaginous structure called a "spike." The causes of this patterning defect in Xenopus frog limb regeneration were explored. We hypothesized that differences in chondrogenesis may underlie the patterning defect. Thus, we focused on chondrogenesis. Chondrogenesis marker genes, type I and type II collagen, were compared in regenerative and nonregenerative environments. There were marked differences between axolotls and Xenopus in the expression pattern of these chondrogenesis-associated genes. The relative deficit in the chondrogenic capacity of Xenopus blastema cells may account for the absence of total limb regenerative capacity.

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  • The Roles of GRASP55/65 in Golgi Formation and Function 査読

    Ayano Satoh, Youko Hasegawa, Yasuko Honjo

    TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY   27 ( 153 )   33 - 36   2015年1月

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    記述言語:英語   出版者・発行元:GAKUSHIN PUBL CO  

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  • Cancer stem cells maintain a hierarchy of differentiation by creating their niche 査読

    Akifumi Mizutani, Shuichi Matsuda, Ting Yan, Marta Prieto-Vila, Ling Chen, Ayano Satoh, Tomonari Kasai, Junko Masuda, Takyuki Kudoh, Hiroshi Murakami, Li Fu, David S. Salomon, Masaharu Seno

    CANCER RESEARCH   74 ( 19 )   2014年10月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2014-3026

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  • Cancer stem cells maintain a hierarchy of differentiation by creating their niche 査読 国際誌

    Shuichi Matsuda, Ting Yan, Akifumi Mizutani, Tatsuyuki Sota, Yuki Hiramoto, Marta Prieto-Vila, Ling Chen, Ayano Satoh, Takayuki Kudoh, Tomonari Kasai, Hiroshi Murakami, Li Fu, David S. Salomon, Masaharu Seno

    INTERNATIONAL JOURNAL OF CANCER   135 ( 1 )   27 - 36   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    The self-renewal and differentiation properties of cancer stem cells (CSCs) are regulated and maintained by the CSC niche. However, the mechanism of this maintenance, especially the maintenance contributed by differentiated cancer cells, remains to be fully elucidated. Recently, we have established a model of CSCs, miPS-LLCcm, from mouse induced pluripotent stem cells (miPSCs). In vitro cultured miPS-LLCcm cells were autonomously balanced with stem-like cells and differentiated cells including vascular endothelial cells. Under these conditions, the CSC properties appeared to be stable in the presence of the factor(s) secreted by the differentiated cells. The factor(s) activated Notch signaling and promoted self-renewal of CSCs. In addition, the secreted factor(s) appeared to regulate the differentiation lineage of CSCs. Our results indicate that the differentiated progenies of CSCs containing vascular endothelium play important roles for regulating the CSC's properties. Therefore, miPS-LLCcm cells create their own in vitro niche to maintain themselves in the hierarchy of differentiating CSCs.

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  • Stabilization of actin bundles by a dynamin 1/cortactin ring complex is necessary for growth cone filopodia. 査読 国際誌

    Hiroshi Yamada, Tadashi Abe, Ayano Satoh, Nana Okazaki, Shota Tago, Kinue Kobayashi, Yumi Yoshida, Yoshiya Oda, Masami Watanabe, Kazuhito Tomizawa, Hideki Matsui, Kohji Takei

    The Journal of neuroscience : the official journal of the Society for Neuroscience   33 ( 10 )   4514 - 26   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Dynamin GTPase, a key molecule in endocytosis, mechanically severs the invaginated membrane upon GTP hydrolysis. Dynamin functions also in regulating actin cytoskeleton, but the mechanisms are yet to be defined. Here we show that dynamin 1, a neuronal isoform of dynamin, and cortactin form ring complexes, which twine around F-actin bundles and stabilize them. By negative-staining EM, dynamin 1-cortactin complexes appeared as "open" or "closed" rings depending on guanine nucleotide conditions. By pyrene actin assembly assay, dynamin 1 stimulated actin assembly in mouse brain cytosol. In vitro incubation of F-actin with both dynamin 1 and cortactin led to the formation of long and thick actin bundles, on which dynamin 1 and cortactin were periodically colocalized in puncta. A depolymerization assay revealed that dynamin 1 and cortactin increased the stability of actin bundles, most prominently in the presence of GTP. In rat cortical neurons and human neuroblastoma cell line, SH-SY5Y, both dynamin 1 and cortactin localized on actin filaments and the bundles at growth cone filopodia as revealed by immunoelectron microscopy. In SH-SY5Y cell, acute inhibition of dynamin 1 by application of dynamin inhibitor led to growth cone collapse. Cortactin knockdown also reduced growth cone filopodia. Together, our results strongly suggest that dynamin 1 and cortactin ring complex mechanically stabilizes F-actin bundles in growth cone filopodia. Thus, the GTPase-dependent mechanochemical enzyme property of dynamin is commonly used both in endocytosis and regulation of F-actin bundles by a dynamin 1-cortactin complex.

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  • Absence of Nogo-B (Reticulon 4B) Facilitates Hepatic Stellate Cell Apoptosis and Diminishes Hepatic Fibrosis in Mice 査読 国際誌

    Keitaro Tashiro, Ayano Satoh, Teruo Utsumi, Chuhan Chung, Yasuko Iwakiri

    AMERICAN JOURNAL OF PATHOLOGY   182 ( 3 )   786 - 795   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Nogo-B (reticulon 4B) accentuates hepatic fibrosis and cirrhosis, but the mechanism remains unclear. The aim of this study was to identify the role of Nogo-B in hepatic stellate cell (HSC) apoptosis in cirrhotic livers. Cirrhosis was generated by carbon tetrachloride inhalation in wild-type (WT) and Nogo-A/B knockout (Nogo-B KO) mice. HSCs were isolated from WT and Nogo-B KO mice and cultured for activation and transformation to myofibroblasts (MF-HSCs). Human hepatic stellate cells (LX2 cells) were used to assess apoptotic responses of activated HSCs after silencing or overexpressing Nogo-B. Livers from cirrhotic Nogo-B KO mice showed significantly reduced fibrosis (P &lt; 0.05) compared with WT mice. Apoptotic cells were more prominent in fibrotic areas of cirrhotic Nogo-B KO livers. Nogo-B KO MF-HSCs showed significantly increased Levels of apoptotic markers, cleaved poly (ADP-ribose) polymerase, and caspase-3 and -8 (P &lt; 0.05) compared with WT MF-HSCs in response to staurosporine. Treatment with tunicamycin, an endoplasmic reticulum stress inducer, increased cleaved caspase-3 and -8 levels in Nogo-B KO MF-HSCs compared with WT MF-HSCs (P &lt; 0.01). In LX2 cells, Nogo-B knockdown enhanced apoptosis in response to staurosporine, whereas Nogo-B overexpression inhibited apoptosis. The absence of Nogo-B enhances apoptosis of HSCs in experimental cirrhosis. Selective blockade of Nogo-B in HSCs may represent a potential therapeutic strategy to mitigate liver fibrosis. (Am J Pathol 2013, 182: 786-795; http://dx.doLorg/10.1016Aajpath.2012.11.032)

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  • The Golgin Tether Giantin Regulates the Secretory Pathway by Controlling Stack Organization within Golgi Apparatus 査読 国際誌

    Mayuko Koreishi, Thomas J. Gniadek, Sidney Yu, Junko Masuda, Yasuko Honjo, Ayano Satoh

    PLOS ONE   8 ( 3 )   e59821   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Golgins are coiled-coil proteins that play a key role in the regulation of Golgi architecture and function. Giantin, the largest golgin in mammals, forms a complex with p115, rab1, GM130, and soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), thereby facilitating vesicle tethering and fusion processes around the Golgi apparatus. Treatment with the microtubule destabilizing drug nocodazole transforms the Golgi ribbon into individual Golgi stacks. Here we show that siRNA-mediated depletion of giantin resulted in more dispersed Golgi stacks after nocodazole treatment than by control treatment, without changing the average cisternal length. Furthermore, depletion of giantin caused an increase in cargo transport that was associated with altered cell surface protein glycosylation. Drosophila S2 cells are known to have dispersed Golgi stacks and no giantin homolog. The exogenous expression of mammalian giantin cDNA in S2 cells resulted in clustered Golgi stacks, similar to the Golgi ribbon in mammalian cells. These results suggest that the spatial organization of the Golgi ribbon is mediated by giantin, which also plays a role in cargo transport and sugar modifications.

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  • CK2 Phosphorylates Sec31 and Regulates ER-To-Golgi Trafficking 査読 国際誌

    Mayuko Koreishi, Sidney Yu, Mayumi Oda, Yasuko Honjo, Ayano Satoh

    PLOS ONE   8 ( 1 )   e54382   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Protein export from the endoplasmic reticulum (ER) is an initial and rate-limiting step of molecular trafficking and secretion. This is mediated by coat protein II (COPII)-coated vesicles, whose formation requires small GTPase Sar1 and 6 Sec proteins including Sec23 and Sec31. Sec31 is a component of the outer layer of COPII coat and has been identified as a phosphoprotein. The initiation and promotion of COPII vesicle formation is regulated by Sar1; however, the mechanism regulating the completion of COPII vesicle formation followed by vesicle release is largely unknown. Hypothesizing that the Sec31 phosphorylation may be such a mechanism, we identified phosphorylation sites in the middle linker region of Sec31. Sec31 phosphorylation appeared to decrease its association with ER membranes and Sec23. Non-phosphorylatable mutant of Sec31 stayed longer at ER exit sites and bound more strongly to Sec23. We also found that CK2 is one of the kinases responsible for Sec31 phosphorylation because CK2 knockdown decreased Sec31 phosphorylation, whereas CK2 overexpression increased Sec31 phosphorylation. Furthermore, CK2 knockdown increased affinity of Sec31 for Sec23 and inhibited ER-to-Golgi trafficking. These results suggest that Sec31 phosphorylation by CK2 controls the duration of COPII vesicle formation, which regulates ER-to-Golgi trafficking.

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  • Transport within the Golgi: For the study of glycoprotein movement 査読

    Ayano Satoh, Yasuko Iwakiri

    Trends in Glycoscience and Glycotechnology   25 ( 146 )   241 - 244   2013年

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    記述言語:英語  

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  • Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells 査読 国際誌

    Sreeja C. Sekhar, Tomonari Kasai, Ayano Satoh, Tsukasa Shigehiro, Akifumi Mizutani, Hiroshi Murakami, Bishoy Y. A. El-Aarag, David S. Salomon, Anna Massaguer, Rafael de Llorens, Masaharu Seno

    JOURNAL OF CANCER   4 ( 5 )   391 - 401   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IVYSPRING INT PUBL  

    The oncogenic tyrosine kinase receptor ErbB2 is a prognostic factor and target for breast cancer therapeutics. In contrast with the other ErbB receptors, ErbB2 is hardly internalized by ligand induced mechanisms, indicating a prevalent surface expression. Elevated levels of ErbB2 in tumor cells are associated with its defective endocytosis and down regulation. Here we show that caveolin-1 expression in breast cancer derived SKBR-3 cells (SKBR-3/Cav-1) facilitates ligand induced ErbB2 endocytosis using an artificial peptide ligand EC-eGFP. Similarly, stimulation with humanized anti ErbB2 antibody Trastuzumab (Herceptin) was found to be internalized and co-localized with caveolin-1 in SKBR-3/Cav-1 cells. Internalized EC-eGFP and Trastuzumab in SKBR-3/Cav-1 cells were then delivered via caveolae to the caveolin-1 containing early endosomes. Consequently, attenuated Fc receptor mediated ADCC functions were observed when exposed to Trastuzumab and EC-Fc (EC-1 peptide conjugated to Fc part of human IgG). On the other hand, this caveolae dependent endocytic synergy was not observed in parental SKBR-3 cells. Therefore, caveolin-1 expression in breast cancer cells could be a predictive factor to estimate how cancer cells are likely to respond to Trastuzumab treatment.

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  • エボラウイルス表層糖タンパク質に対する糖鎖修飾制御メカニズムの解明

    藤平 陽彦, 宇佐美 克明, 伝田 香里, 松野 啓太, 篠原 康郎, 佐藤 あやの, 高田 礼人, 入村 達郎

    日本生化学会大会プログラム・講演要旨集   85回   3T15 - 08   2012年12月

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    記述言語:日本語   出版者・発行元:(公社)日本生化学会  

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  • A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells 査読 国際誌

    Ling Chen, Tomonari Kasai, Yueguang Li, Yuh Sugii, Guoliang Jin, Masashi Okada, Arun Vaidyanath, Akifumi Mizutani, Ayano Satoh, Takayuki Kudoh, Mary J. C. Hendrix, David S. Salomon, Li Fu, Masaharu Seno

    PLOS ONE   7 ( 4 )   e33544   2012年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Cancer stem cells (CSCs) are capable of continuous proliferation and self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. CSCs are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka's group succeeded in generating Nanog mouse induced pluripotent stem (miPS) cells, in which green fluorescent protein (GFP) has been inserted into the 5'-untranslated region of the Nanog gene. Usually, iPS cells, just like embryonic stem cells, are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that CSCs could be derived from Nanog miPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the Nanog miPS cells treated with the conditioned medium of mouse Lewis lung carcinoma acquired characteristics of CSCs, in that they formed spheroids expressing GFP in suspension culture, and had a high tumorigenicity in Balb/c nude mice exhibiting angiogenesis in vivo. In addition, these iPS-derived CSCs had a capacity of self-renewal and expressed the marker genes, Nanog, Rex1, Eras, Esg1 and Cripto, associated with stem cell properties and an undifferentiated state. Thus we concluded that a model of CSCs was originally developed from miPS cells and proposed the conditioned culture medium of cancer cell lines might perform as niche for producing CSCs. The model of CSCs and the procedure of their establishment will help study the genetic alterations and the secreted factors in the tumor microenvironment which convert miPS cells to CSCs. Furthermore, the identification of potentially bona fide markers of CSCs, which will help the development of novel anti-cancer therapies, might be possible though the CSC model.

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  • TRAPPC9 Mediates the Interaction between p150(Glued) and COPII Vesicles at the Target Membrane 査読 国際誌

    Min Zong, Ayano Satoh, Mei Kuen Yu, Ka Yu Siu, Wing Yan Ng, Hsiao Chang Chan, Julian A. Tanner, Sidney Yu

    PLOS ONE   7 ( 1 )   e29995   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: The transport of endoplasmic reticulum (ER)-derived COPII vesicles toward the ER-Golgi intermediate compartment (ERGIC) requires cytoplasmic dynein and is dependent on microtubules. p150(Glued), a subunit of dynactin, has been implicated in the transport of COPII vesicles via its interaction with COPII coat components Sec23 and Sec24. However, whether and how COPII vesicle tether, TRAPP (Transport protein particle), plays a role in the interaction between COPII vesicles and microtubules is currently unknown.
    Principle Findings: We address the functional relationship between COPII tether TRAPP and dynactin. Overexpressed TRAPP subunits interfered with microtubule architecture by competing p150(Glued) away from the MTOC. TRAPP subunit TRAPPC9 bound directly to p150(Glued) via the same carboxyl terminal domain of p150(Glued) that binds Sec23 and Sec24. TRAPPC9 also inhibited the interaction between p150(Glued) and Sec23/Sec24 both in vitro and in vivo, suggesting that TRAPPC9 serves to uncouple p150(Glued) from the COPII coat, and to relay the vesicle-dynactin interaction at the target membrane.
    Conclusions: These findings provide a new perspective on the function of TRAPP as an adaptor between the ERGIC membrane and dynactin. By preserving the connection between dynactin and the tethered and/or fused vesicles, TRAPP allows nascent ERGIC to continue the movement along the microtubules as they mature into the cis-Golgi.

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  • Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand 査読 国際誌

    Arun Vaidyanath, Toshihiro Hashizume, Tadahiro Nagaoka, Nao Takeyasu, Hitomi Satoh, Ling Chen, Jiyou Wang, Tomonari Kasai, Takayuki Kudoh, Ayano Satoh, Li Fu, Masaharu Seno

    JOURNAL OF CELLULAR AND MOLECULAR MEDICINE   15 ( 11 )   2525 - 2538   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Targeting and down-regulation of ErbB2, a member of EGF receptor family, is regarded as one of the key aspect for cancer treatment because it is often overexpressed in breast and ovarian cancer cells. Although natural ligands for ErbB2 have not been found, unlike other ErbB receptors, EC-1, a 20-amino acid circular peptide, has been shown to bind to ErbB2 as an artificial ligand. Previously we showed EC-1 peptide did not induce the internalization of ErbB2 in SK-BR-3 cells. In this report, we designed divalent and multivalent forms of EC-1 peptide with the Fc portion of the human IgG and bionanocapsule modified with ZZ-tag on its surface to improve the interaction with ErbB2. These forms showed higher affinity to ErbB2 than that of EC-1 monomer. Furthermore, prominent endosomal accumulation of ErbB2 occurred in SK-BR-3 cells when stimulated with EC-Fc ligand multivalently displayed on the surface of the bionanocapsule, whereas SK-BR-3 cells as themselves displayed stringent mechanism against ErbB2 internalization without stimulation. The multivalent form of EC-1 peptide appeared to internalize ErbB2 more efficiently than divalent form did. This internalization was unaffected by the inhibition of clathrin association, but inhibited when the cholesterol was depleted which explained either caveolar or GPI-AP-early endocytic compartment (GEEC) pathway. Because of the lack of caveolin-1 expression, caveolar machinery may be lost in SK-BR-3 cell line. Therefore, it is suggested that the multivalent form of EC-1 induces the internalization of ErbB2 through the GEEC pathway.

    DOI: 10.1111/j.1582-4934.2011.01277.x

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  • Abnormal Trafficking and Degradation of TLR4 Underlie the Elevated Inflammatory Response in Cystic Fibrosis 査読 国際誌

    Emanuela M. Bruscia, Ping-Xia Zhang, Ayano Satoh, Christina Caputo, Ruslan Medzhitov, Ambika Shenoy, Marie E. Egan, Diane S. Krause

    JOURNAL OF IMMUNOLOGY   186 ( 12 )   6990 - 6998   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC IMMUNOLOGISTS  

    Morbidity and mortality in cystic fibrosis (CF) are due not only to abnormal epithelial cell function, but also to an abnormal immune response. We have shown previously that macrophages lacking CF transmembrane conductance regulator (CFTR), the gene mutated in CF, contribute significantly to the hyperinflammatory response observed in CF. In this study, we show that lack of functional CFTR in murine macrophages causes abnormal TLR4 subcellular localization. Upon LPS stimulation, CFTR macrophages have prolonged TLR4 retention in the early endosome and reduced translocation into the lysosomal compartment. This abnormal TLR4 trafficking leads to increased LPS-induced activation of the NF-kappa B, MAPK, and IFN regulatory factor-3 pathways and decreased TLR4 degradation, which affects downregulation of the proinflammatory state. In addition to primary murine cells, mononuclear cells isolated from CF patients demonstrate similar defects in response to LPS. Moreover, specific inhibition of CFTR function induces abnormal TLR4 trafficking and enhances the inflammatory response of wild-type murine cells to LPS. Thus, functional CFTR in macrophages influences TLR4 spatial and temporal localization and perturbs LPS-mediated signaling in both murine CF models and patients with CF. The Journal of Immunology, 2011, 186: 6990-6998.

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  • Detection of in situ cleaved p115 with the cut specific antibodies in rapid protein inactivation system by tobacco etch viral protease cleavage 査読

    Koreyoshi Mayuko, Honjo Yasuko, Satoh Ayano

    Antibody Technology Journal   2011 ( 1 )   5 - 11   2011年

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  • mTrs130 Is a Component of a Mammalian TRAPPII Complex, a Rab1 GEF That Binds to COPI-coated Vesicles 査読 国際誌

    Akinori Yamasaki, Shekar Menon, Sidney Yu, Jemima Barrowman, Timo Meerloo, Viola Oorschot, Judith Klumperman, Ayano Satoh, Susan Ferro-Novick

    MOLECULAR BIOLOGY OF THE CELL   20 ( 19 )   4205 - 4215   2009年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC CELL BIOLOGY  

    The GTPase Rab1 regulates endoplasmic reticulum-Golgi and early Golgi traffic. The guanine nucleotide exchange factor (GEF) or factors that activate Rab1 at these stages of the secretory pathway are currently unknown. Trs130p is a subunit of the yeast TRAPPII (transport protein particle II) complex, a multisubunit tethering complex that is a GEF for the Rab1 homologue Ypt1p. Here, we show that mammalian Trs130 (mTrs130) is a component of an analogous TRAPP complex in mammalian cells, and we describe for the first time the role that this complex plays in membrane traffic. mTRAPPII is enriched on COPI (Coat Protein I)-coated vesicles and buds, but not Golgi cisternae, and it specifically activates Rab1. In addition, we find that mTRAPPII binds to gamma 1COP, a COPI coat adaptor subunit. The depletion of mTrs130 by short hairpin RNA leads to an increase of vesicles in the vicinity of the Golgi and the accumulation of cargo in an early Golgi compartment. We propose that mTRAPPII is a Rab1 GEF that tethers COPI-coated vesicles to early Golgi membranes.

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  • Following the Fate In Vivo of COPI Vesicles Generated In Vitro 査読 国際誌

    Christoph Rutz, Ayano Satoh, Paolo Ronchi, Britta Bruegger, Graham Warren, Felix T. Wieland

    TRAFFIC   10 ( 8 )   994 - 1005   2009年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    COPI vesicles are a class of transport carriers that function in the early secretory pathway. Their fate and function are still controversial. This includes their contribution to bidirectional transport within the Golgi apparatus and their role during cell division. Here we describe a method that should address several open questions about the fate and function of COPI vesicles in vivo. To this end, fluorescently labeled COPI vesicles were generated in vitro from isolated rat liver Golgi membranes, labeled with the fluorescent dyes Alexa-488 or Alexa-568. These vesicles appeared to be active and colocalized with endogenous Golgi membranes within 30 min after microinjection into mammalian cells. The COPI vesicle-derived labeled membrane proteins could be classified into two types that behaved like endogenous proteins after Brefeldin A treatment.

    DOI: 10.1111/j.1600-0854.2009.00934.x

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  • A PDZ-Binding Motif Controls Basolateral Targeting of Syndecan-1 Along the Biosynthetic Pathway in Polarized Epithelial Cells 査読 国際誌

    Sandra Maday, Eric Anderson, Henry C. Chang, James Shorter, Ayano Satoh, Jeff Sfakianos, Heike Folsch, James M. Anderson, Zenta Walther, Ira Mellman

    TRAFFIC   9 ( 11 )   1915 - 1924   2008年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    The cell surface proteoglycan, syndecan-1, is essential for normal epithelial morphology and function. Syndecan-1 is selectively localized to the basolateral domain of polarized epithelial cells and interacts with cytosolic PDZ (PSD-95, discs large, ZO-1) domain-containing proteins. Here, we show that the polarity of syndecan-1 is determined by its type II PDZ-binding motif. Mutations within the PDZ-binding motif lead to the mislocalization of syndecan-1 to the apical surface. In contrast to previous examples, however, PDZ-binding motif-dependent polarity is not determined by retention at the basolateral surface but rather by polarized sorting prior to syndecan1's arrival at the plasma membrane. Although none of the four known PDZ-binding partners of syndecan-1 appears to control basolateral localization, our results show that the PDZ-binding motif of syndecan-1 is decoded along the biosynthetic pathway establishing a potential role for PDZ-mediated interactions in polarized sorting.

    DOI: 10.1111/j.1600-0854.2008.00805.x

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  • In situ cleavage of the acidic domain from the p115 tether inhibits exocytic transport 査読 国際誌

    Ayano Satoh, Graham Warren

    TRAFFIC   9 ( 9 )   1522 - 1529   2008年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Golgins are coiled-coil proteins involved in Golgi architecture and function. A complex of golgins (p115, GM130 and giantin), together with the rab1 guanosine triphosphatase and cis Golgi SNAREs, helps to mediate fusion processes at the entry face of the Golgi apparatus. The C-terminal acidic domain of p115 binds specifically to GM130 and giantin. However, deletion of this domain in vivo appears to have no effect on exocytic transport when using an RNA interference depletion/rescue approach (Puthenveedu MA, Linstedt AD. Gene replacement reveals that p115/SNARE interactions are essential for Golgi biogenesis. Proc Natl Acad Sci U S A 2004;101:1253-1256). In this study, we have used a different approach introducing a tobacco etch virus (tev) protease cleavage site into p115 so that the C-terminal domain can be rapidly and specifically released in vivo by microinjection of the tev protease. The results show that cleavage inhibits exocytic transport to the cell surface.

    DOI: 10.1111/j.1600-0854.2008.00783.x

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  • Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors 査読 国際誌

    Xiaoxiao Pan, Anja Luhrmann, Ayano Satoh, Michelle A. Laskowski-Arce, Craig R. Roy

    SCIENCE   320 ( 5883 )   1651 - 1654   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC ADVANCEMENT SCIENCE  

    Specialized secretion systems are used by many bacteria to deliver effector proteins into host cells that can either mimic or disrupt the function of eukaryotic factors. We found that the intracellular pathogens Legionella pneumophila and Coxiella burnetii use a type IV secretion system to deliver into eukaryotic cells a large number of different bacterial proteins containing ankyrin repeat homology domains called Anks. The L. pneumophila AnkX protein prevented microtubule- dependent vesicular transport to interfere with fusion of the L. pneumophila- containing vacuole with late endosomes after infection of macrophages, which demonstrates that Ank proteins have effector functions important for bacterial infection of eukaryotic host cells.

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  • Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking 査読 国際誌

    Yasuko Iwakiri, Ayano Satoh, Suvro Chatterjee, Derek K. Toomre, Cecile M. Chalouni, David Fulton, Roberto J. Groszmann, Vijay H. Shah, William C. Sessa

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   103 ( 52 )   19777 - 19782   2006年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATL ACAD SCIENCES  

    Nitric oxide (NO) is a highly diffusible and short-lived physiological messenger. Despite its diffusible nature, NO modifies thiol groups of specific cysteine residues in target proteins and alters protein function via S-nitrosylation. Although intracellular S-nitrosylation is a specific posttranslational modification, the defined localization of an NO source (nitric oxide synthase, NOS) with protein S-nitrosylation has never been directly demonstrated. Endothelial NOS (eNOS) is localized mainly on the Golgi apparatus and in plasma membrane caveolae. Here, we show by using eNOS targeted to either the Golgi or the nucleus that S-nitrosylation is concentrated at the primary site of eNOS localization. Furthermore, localization of eNOS on the Golgi enhances overall Golgi protein S-nitrosylation, the specific S-nitrosylation of N-ethylmaleimide-sensitive factor and reduces the speed of protein transport from the endoplasmic reticulum to the plasma membrane in a reversible manner. These data indicate that local NOS action generates organelle-specific protein S-nitrosylation reactions that can regulate intracellular transport processes.

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  • MBet3p is required for homotypic COPII vesicle tethering in mammalian cells 査読 国際誌

    Sidney Yu, Ayano Satoh, Marc Pypaert, Karl Mullen, Jesse C. Hay, Susan Ferro-Novick

    JOURNAL OF CELL BIOLOGY   174 ( 3 )   359 - 368   2006年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROCKEFELLER UNIV PRESS  

    TRAPPI is a large complex that mediates the tethering of COPII vesicles to the Golgi (heterotypic tethering) in the yeast Saccharomyces cerevisiae. In mammalian cells, COPII vesicles derived from the transitional endoplasmic reticulum (tER) do not tether directly to the Golgi, instead, they appear to tether to each other ( homotypic tethering) to form vesicular tubular clusters (VTCs). We show that mammalian Bet3p (mBet3p), which is the most highly conserved TRAPP subunit, resides on the tER and adjacent VTCs. The inactivation of mBet3p results in the accumulation of cargo in membranes that colocalize with the COPII coat. Furthermore, using an assay that reconstitutes VTC biogenesis in vitro, we demonstrate that mBet3p is required for the tethering and fusion of COPII vesicles to each other. Consistent with the proposal that mBet3p is required for VTC biogenesis, we find that ERGIC-53 ( VTC marker) and Golgi architecture are disrupted in siRNA-treated mBet3p-depleted cells. These findings imply that the TRAPPI complex is essential for VTC biogenesis.

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  • Beta-2-glycoprotein I and urinary trypsin inhibitor levels in the plasma of pregnant and postpartum women 査読 国際誌

    J Masuda, K Suzuki, A Satoh, K Kojima-Aikawa, K Nakanishi, K Kuroda, M Murakami, E Takayama, Matsumoto, I

    THROMBOSIS RESEARCH   117 ( 3 )   255 - 261   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Annexins (Anx) are a family of structurally related proteins that all, bind to anionic phospholipids in a Ca2+-dependent manner. Some biological properties of beta-2-glycoprotein I (beta(2)-GPI) are similar to those of Anx IV and Anx V. Urinary trypsin inhibitor (UTI) helps to maintain normal pregnancy and prevent preterm delivery by inhibiting uterine contraction. However, plasma beta(2)-GPI and UTI levels have not been measured in normal pregnancy. The aim of this study is to clarify the levels of these parameters. Subjects were nonpregnant women (n = 50), 120 pregnant women, and maternal subjects just after delivery (n = 53) or postpartum (n = 67). All of the subjects were healthy. Plasma levels of beta(2)-GPI, UTI, Anx IV, Anx V and other coagulation and fibrinolysis markers were measured by ELISA. The mean plasma level Of beta(2)-GPI was significantly increased during the third trimester of pregnancy and 3 to 5 days after delivery. The mean plasma level of UTI Novas unchanged from the first trimester of pregnancy to the postpartum period. The mean plasma UTI level in vaginal delivery group was significantly higher than that in cesarean section group. beta(2)-GPI protein was expressed in some of the syncytiotrophoblasts. These data suggest that beta(2)-GPI might act to prevent blood clotting on the placental surfaces and also prevents disseminated intravascular coagulation in the microcirculation and maternal plasma. UTI Levels might be kept constant by increased urinary excretion despite overproduction during pregnancy. (c) 2005 Elsevier Ltd. All rights reserved.

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  • A cryptic Rab1-binding site in the p115 tethering protein 査読 国際誌

    M Beard, A Satoh, J Shorter, G Warren

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 27 )   25840 - 25848   2005年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Small GTPases and coiled- coil proteins of the golgin family help to tether COPI vesicles to Golgi membranes. At the cis- side of the Golgi, the Rab1 GTPase binds directly to each of three coiled- coil proteins: p115, GM130, and as now shown, Giantin. Rab1 binds to a coiled- coil region within the tail domain of p115 and this binding is inhibited by the C- terminal, acidic domain of p115. Furthermore, GM130 and Giantin bind to the acidic domain of p115 and stimulate p115 binding to Rab1, suggesting that p115 binding to Rab1 is regulated. Regulation of this interaction by proteins such as GM130 and Giantin may control the membrane recruitment of p115 by Rab1.

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  • Annexins I and IV inhibit Staphylococcus aureus attachment to human macrophages 査読 国際誌

    M Gotoh, Y Takamoto, K Kurosaka, J Masuda, M Ida, A Satoh, E Takayamac, K Kojima-Aikawa, Y Kobayashi, Matsumoto, I

    IMMUNOLOGY LETTERS   98 ( 2 )   297 - 302   2005年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Annexins are a family of proteins that bind to phospholipids and carbohydrates in a calcium-dependent manner. They are present in a variety of body fluids. Previous studies have shown that annexins have anti-inflammatory activities for lipid A of Gram-negative bacteria.
    The present study investigated the effect of annexins on interaction between Gram-positive bacteria and immune cells such as macrophages. Annexins I and IV bound to lipoteichoic acids which are surface molecules on Gram-positive bacteria. Binding of annexins I and IV to whole Staphylococcus aureus (S. aureus) were observed and these bindings were inhibited by lipoteichoic acid from S. aureus. Moreover, annexins I and IV suppressed the attachment of S. aureus to phorbol 12-myristate 13-acetate-treated THP-1 cells (human macrophages). These results suggest that annexins I and IV have ligand specificities toward foreign substances, and that the annexins might have some anti-inflammatory property for Gram-positive bacteria. (c) 2004 Elsevier B.V. All rights reserved.

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  • Mapping the functional domains of the Golgi stacking factor GRASP65 査読 国際誌

    YZ Wang, A Satoh, G Warren

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 6 )   4921 - 4928   2005年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    The Golgi reassembly stacking protein (GRASP) family has been implicated in the stacking of Golgi cisternae and the regulation of Golgi disassembly/reassembly during mitosis in mammalian cells. GRASP65 is a dimer that can directly link adjacent surfaces through trans-oligomerization in a mitotically regulated manner. Here we show that the N-terminal GRASP domain (amino acids 1-201) is both necessary and sufficient for dimerization and trans-oligomerization but is not mitotically regulated. The C-terminal serine/proline-rich domain (amino acids 202-446) cannot dimerize nor can it link adjacent surfaces. It does, however, confer mitotic regulation on the GRASP domain through multiple sites phosphorylated by the mitotic kinases, cdc2/B1, and the polo-like kinase. Transient expression corroborated these results by showing that the GRASP domain alone inhibited mitotic fragmentation of the Golgi apparatus.

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  • Goigin tethers define subpopulations of COPI vesicles 査読 国際誌

    J Malsam, A Satoh, L Pelletier, G Warren

    SCIENCE   307 ( 5712 )   1095 - 1098   2005年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC ADVANCEMENT SCIENCE  

    Coiled-coil proteins of the golgin family have been implicated in intra-Golgi transport through tethering coat protein complex I (COPI) vesicles. The p115-golgin tether is the best studied, and here we characterize the golgin-84-CASP tether. The vesicles bound by this tether were strikingly different from those bound by the p115-golgin tether in that they lacked members of the p24 family of putative cargo receptors and contained enzymes instead of anterograde cargo. Microinjected golgin-84 or CASP also inhibited Golgi-enzyme transport to the endoplasmic reticulum, further implicating this tether in retrograde transport. These and other golgins may modulate the flow patterns within the Golgi stack.

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  • Tethering assays for COPI vesicles mediated by golgins 査読 国際誌

    A Satoh, J Malsam, G Warren

    GTPASES REGULATING MEMBRANE DYNAMICS   404   125 - 134   2005年

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:ELSEVIER ACADEMIC PRESS INC  

    A method is described that allows the attachment of COPI vesicles and Golgi membranes to glass slides that can then be analyzed using electron microscopy (EM) and immuno-EM methods. Subpopulations of COPI vesicles can be bound selectively using recombinant golgins. Alternatively, COPI vesicles can be attached to prebound Golgi membranes. Marking these vesicles selectively with biotin allows their site of attachment to be identified.

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  • Preparation and characterization of recombinant golgin tethers 査読 国際誌

    A Satoh, M Beard, G Warren

    GTPASES REGULATING MEMBRANE DYNAMICS   404   279 - 296   2005年

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:ELSEVIER ACADEMIC PRESS INC  

    Golgin tethers are integral or peripheral Golgi proteins with predicted coiled-coil domains and many are known to interact directly with small GTPases of the Ypt/Rab or Arl families. Here we describe the preparation of recombinant golgins: GM130, p115 (and truncations thereof), the N-terminal fragment of giantin, CASP, and golgin-84.

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  • A novel expression vector, designated as pHisJM, for producing recombinant His-fusion proteins 査読 国際誌

    J Masuda, E Takayama, A Satoh, K Kojima-Aikawa, K Suzuki, Matsumoto, I

    BIOTECHNOLOGY LETTERS   26 ( 20 )   1543 - 1548   2004年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KLUWER ACADEMIC PUBL  

    Compared to glutathione S-transferase (GST), tagging with hexahistidine residues (His) has several merits: low levels of toxicity and immunogenicity, a smaller size and no electric charge. We have constructed a novel expression vector, designated as pHisJM (EMBL/GenBank/DDJB accession no. AB 116367), for producing recombinant His-fusion proteins. This vector was constructed by replacing GST and multiple cloning site (MCS) cassettes in pGEX-5X-3 with those of hexahistidine and MCS derived from pRSET C vector. Human annexin IV (Anx IV) was used as target protein. His-Anx IV fusion protein was expressed using pHisJM and gave a 40 kDa band when immuno-stained with anti-His mAb or anti-Anx IV mAb as predicted. To compare expression efficiency, a Anx IV cDNA inserted-pHisJM or pGEX-5X-3 was transformed into Escherichia coli DH5alpha, JM109, BL21 and BL21(DE3). Using pHisJM, Anx IV protein was highly expressed in all cell strains. In addition to the merits of using His-tag, pHisJM has several advantages: 1) it has high expression efficiency; 2) it can be used in any Escherichia coli strain; and 3) it can be used in a single strain of Escherichia coli in all steps from plasmid construction to the expression of the target gene.

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  • Levels of annexin IV and V in the plasma of pregnant and postpartum women 査読 国際誌

    J Masuda, E Takayama, A Satoh, M Ida, T Shinohara, K Kojima-Aikawa, F Ohsuzu, K Nakanishi, K Kuroda, M Murakami, K Suzuki, Matsumoto, I

    THROMBOSIS AND HAEMOSTASIS   91 ( 6 )   1129 - 1136   2004年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

    Annexin (Anx) V is pivotal in the maintenance of pregnancy by preventing the activation of blood coagulation. The homology of the amino acid sequence between Anx IV and Anx V is highest in Anx family proteins. However, little is known about the roles of Anx IV in pregnancy. The aim of this study is to clarify the roles of circulating Anx IV and Anx V in normal pregnancy. Subjects were non-pregnant women (n = 50), 120 pregnant women, and maternal subjects just after delivery (n = 53) or postpartum (n = 67). Anx IV in the plasma of non-pregnant women was at a concentration 20 times that of AnxV. The plasma levels of Anx IV suddenly increase after delivery, but Anx V levels remain low during this period. Anx IV and Anx V exert similar levels of anticoagulant activity. Anx IV protein was expressed on the basal surface of syncytiotrophoblasts; Anx V protein, on the apical surface of syncytiotrophoblasts. These results suggest that Anx IV enters the maternal bloodstream just after delivery and might play a role in preventing disseminated intravascular coagulopathy, and that Anx V helps to prevent clotting in the placenta during pregnancy.

    DOI: 10.1160/TH03-12-0778

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  • Human annexin V binds to sulfatide: Contribution to regulation of blood coagulation 査読 国際誌

    M Ida, A Satoh, Matsumoto, I, K Kojima-Aikawa

    JOURNAL OF BIOCHEMISTRY   135 ( 5 )   583 - 588   2004年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPANESE BIOCHEMICAL SOC  

    Annexin V is a calcium-dependent phospholipid-binding protein that exhibits anticoagulant activity on binding to phosphatidylserine exposed on the activated surfaces of endothelial cells and platelets, inhibiting activation of factor X and prothrombin in the blood coagulation cascade. Sulfatide (galactosylceramide I-3-sulfate), one of the glycosphingolipids of the platelet cell membrane, is thought to be involved in blood coagulation systems via activation of factor XII. In this study, we examined whether or not annexin V binds to sulfatide and affects the coagulant activity of sulfatide. Solid phase assaying of annexin V revealed that it binds specifically to sulfatide, i.e. not to galactosylceramide or gangliosides, in the presence of calcium ions. Affinity analysis by means of surface plasmon resonance showed that the K-D of the interaction between annexin V and sulfatide is 1.2 muM. Kinetic turbidometric assaying of plasma coagulation initiated by CaCl2 revealed that the coagulation rate in the presence of sulfatide or phosphatidylserine was decreased by annexin V. These results suggest that annexin V regulates coagulability in the blood stream by binding not only to phosphatidylserine but also to sulfatide.

    DOI: 10.1093/jb/mvh071

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  • VCIP135 acts as a deubiquitinating enzyme during p97-p47-mediated reassembly of mitotic Golgi fragments 査読 国際誌

    YZ Wang, A Satoh, G Warren, HH Meyer

    JOURNAL OF CELL BIOLOGY   164 ( 7 )   973 - 978   2004年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROCKEFELLER UNIV PRESS  

    The AAA-ATPase p97/Cdc48 functions in different cellular pathways using distinct sets of adapters and other cofactors. Together with its adaptor Ufd1-Npl4, it extracts ubiquitylated substrates from the membrane for subsequent delivery to the proteasome during ER-associated degradation. Together with its adaptor p47, on the other hand, it regulates several membrane fusion events, including reassembly of Golgi cisternae after mitosis. The finding of a ubiquitin-binding domain in p47 raises the question as to whether the ubiquitin-proteasome system is also involved in membrane fusion events. Here, we show that p97-p47-mediated reassembly of Golgi cisternae requires ubiquitin, but is not dependent on proteasome-mediated proteolysis. Instead, it requires the deubiquitinating activity of one of its cofactors, VCIP135, which reverses a ubiquitylation event that occurs during mitotic disassembly. Together, these data reveal a cycle of ubiquitylation and deubiquitination that regulates Golgi membrane dynamics during mitosis. Furthermore, they represent the first evidence for a proteasome-independent function of p97/Cdc48.

    DOI: 10.1083/jcb.200401010

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  • Golgin-84 is a Rab1 binding partner involved in Golgi structure 査読 国際誌

    A Satoh, Y Wang, J Malsam, MB Beard, G Warren

    TRAFFIC   4 ( 3 )   153 - 161   2003年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL MUNKSGAARD  

    Members of the golgin family of coiled-coil proteins have been implicated in the tethering of vesicles to Golgi membranes and cisternal membranes to each other. Many also bind to rab GTPases. Golgin-84 is a membrane-anchored golgin that we now show binds preferentially to the GTP form of the rab1 GTPase. It is also present throughout the Golgi stack by immuno-EM. Antibodies to golgin-84 inhibit stacking of cisternal membranes in a cell-free assay for Golgi reassembly, whereas the cytoplasmic domain of golgin-84 stimulates stacking and increases the length of re-assembled stacks. Transient expression of golgin-84 in NRK cells helps prevent the disassembly of the Golgi apparatus normally triggered by treatment with brefeldin A. Together these data suggest that golgin-84 is involved in generating and maintaining the architecture of the Golgi apparatus.

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  • Ligand-binding properties of annexin from Caenorhabditis elegans (annexin XVI, Nex-1) 査読

    A Satoh, M Hazuki, K Kojima, J Hirabayashi, Matsumoto, I

    JOURNAL OF BIOCHEMISTRY   128 ( 3 )   377 - 381   2000年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPANESE BIOCHEMICAL SOC  

    Annexins are structurally related proteins that bind phospholipids in a calcium-dependent manner. Recently, we showed that annexins IV V, and VI also bind glycosaminoglycans in a calcium-dependent manner. Annexins are widely distributed from lower to higher eukaryotes, and the nematode Caenorhabditis elegans has been. found to contain Nex-1, an annexin homologue, Here, we characterize the ligand-binding properties of Nex-1 using recombinant Nex-1. Nex-1 binds to liposomes containing phosphatidylserine. The apparent K-d was calculated by Biacore to be 4.4 nM. Compared to mammalian annexins, the Nex-1 phospholipid-binding specificities were similar whereas the K-d values were one order of magnitude larger. The Nex-1 glycosaminoglycan-binding specificities were investigated by affinity chromatography and solid-phase assays. Nex-1 binds to heparin, heparan sulfate, and chondroitin sulfate but not to chondroitin and chemically N- or O-desulfated heparin, Besides phospholipids, heparan sulfate and/or chondroitin (sulfate), probably on perlecan, could be endogenous ligands of Nex-1.

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  • New role of glycosaminoglycans on the plasma membrane proposed by their interaction with phosphatidylcholine 査読

    A Satoh, T Toida, K Yoshida, K Kojima, Matsumoto, I

    FEBS LETTERS   477 ( 3 )   249 - 252   2000年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Glycosaminoglycan side chains of membrane proteoglycans have been claimed to be located at the outermost layer of the glycocalyx surrounding the cell. In this study measurements by surface plasmon resonance and solid-phase assay have shown that both chondroitin sulfate and keratan sulfate but not heparin associate with phosphatidylcholine under physiological conditions. Spectrophotometric measurements also showed that chondroitin sulfate restricts the lateral diffusion of phosphatidylcholine in liposomes, These findings indicate that chondroitin sulfate and/or keratan sulfate chains of membrane proteoglycans crouch on the surface of the membrane while heparan sulfate chains stretch outward from the membrane surface as postulated traditionally, (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V, All rights reserved.

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MISC

  • Reporter Gene Expression in Heterosigma akashiwo which is a Causative Organism of the Harmful Algal Bloom

    Nanami Nakayama, Ayano Satoh, Shoko Ueki

    MOLECULAR BIOLOGY OF THE CELL /CELL BIO virtual 2020   2020年12月

  • Pancreatic alpha-amylase controls glucose assimilation in duodenum through N-glycan-specific binding, followed by endocytosis and degradation

    Kimie Date, Ayano Satoh, Haruko Ogawa

    GLYCOBIOLOGY   24 ( 11 )   1185 - 1185   2014年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • Development and characterization of cancer stem cell model from mouse iPS cells

    Ling Chen, Shuichi Matsuda, Tomonari Kasai, Yuh Sugii, Masashi Okada, Koichi Igarashi, Ayano Satoh, Takayuki Kudoh, Takayuki Kudoh, Li Fu, Masaharu Seno

    CANCER RESEARCH   72   2012年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2012-418

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  • A cryptic Rab1-binding site in the p115 tethering protein (vol 280, pg 25840, 2005)

    Matthew Beard, Ayano Satoh, James Shorter, Graham Warren

    JOURNAL OF BIOLOGICAL CHEMISTRY   281 ( 38 )   28488 - 28488   2006年9月

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    記述言語:英語   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

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  • Sub-fractionation of COPI vesicles using golgin tethers

    A Satoh, J Malsam, L Pelletier, G Warren

    MOLECULAR BIOLOGY OF THE CELL   15   5A - 5A   2004年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

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  • Ligand-Binding properties of annexin from Caenorhabditis elegans (Annexin XVI, Nex-1) (vol 128, pg 377, 2000)

    A Satoh, M Hazuki, K Kojima, J Hirabayashi, Matsumoto, I

    JOURNAL OF BIOCHEMISTRY   136 ( 3 )   407 - 407   2004年9月

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    記述言語:英語   出版者・発行元:JAPANESE BIOCHEMICAL SOC  

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  • VCIP135 acts as a deubiquitinating enzyme during p97-p47-mediated reassembly of mitotic Golgi fragments (vol. 164, Pg. 973, 2004)

    YZ Wang, A Satoh, G Warren, HH Meyer

    JOURNAL OF CELL BIOLOGY   166 ( 3 )   433 - 433   2004年8月

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    記述言語:英語   出版者・発行元:ROCKEFELLER UNIV PRESS  

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  • Management of a Jehovah's Witness with thrombotic thrombocytopaenic purpura/haemolytic uraemic syndrome

    Kimihiro Suzuki, Ayano Satoh, Toshihiko Hidaka, Eiji Takayama, Kouji Kataharada, Mitsuyo Matsumoto, Tadashi Shinohara, Isamu Matsumoto, Fumitaka Ohsuzu

    Journal of Clinical Apheresis   15 ( 4 )   266 - 267   2000年

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)  

    DOI: 10.1002/1098-1101(2000)15:4<266::AID-JCA9>3.0.CO;2-9

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  • Autoantibodies to annexins IV and V in patients with systemic lupus erythematosus and/or antiphospholipid syndrome

    K Suzuki, A Satoh, E Takayama, M Kawakami, T Hidaka, K Kojima, Matsumoto, I

    ARTHRITIS AND RHEUMATISM   41 ( 9 )   S171 - S171   1998年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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講演・口頭発表等

  • Immunosuppression Effect by Adipose Tissue-derived Mesenchymal Stem Cells Isolated from β2-microglobulin Deficient mice

    第19回武田科学振興財団生命科学シンポジウム  2017年 

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  • ERGIC53のS-ニトロシル化はカーゴタンパク質の分泌に影響する

    第69回日本細胞生物学会大会  2017年 

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  • 哺乳類細胞におけるロバストネス解析を行う実験系の確立

    第69回日本細胞生物学会大会  2017年 

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  • カーゴタンパク質ERGIC53のS-ニトロシル化とその機能解析

    第36回日本糖質学会年会  2017年 

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  • S-ニトロシル化ERGIC-53の機能解析

    第68回日本細胞生物学会大会  2016年 

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  • グルカン結合性タンパク質laforinの一酸化窒素による修飾とLafora病への関与

    第35回日本糖質学会年会  2016年 

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  • cODC1デグロンによるオルガネラ局在観察の改良

    酵母遺伝学フォーラム第49回研究会  2016年 

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  • Sulfonated reduced graphene oxide as a solid acid catalyst

    Catalysis and Fine Chemicals 2016  2016年 

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  • S-ニトロシル化ERGIC-53の機能と局在

    第39回日本分子生物学会年会  2016年 

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  • 新規ビスインドール化合物による分泌阻害の機序解明

    第68回日本細胞生物学会大会  2016年 

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  • Interaction of pancreatic α-amylase with its identified glycoligand SGLT1

    ICS2016 (XXVIII International Carbohydrate symposium)  2016年 

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  • Transient Tcf3 Gene Repression by TALE-Transcription Factor Targeting

    第39回日本分子生物学会年会  2016年 

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  • S-nitrosylation of Laforin inhibits its phosphatase activity and is implicated in Lafora disease

    第56回アメリカ細胞生物学会年会  2016年 

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  • ハイスループットスクリーニングによるフルオロアルキル基を有するビスインドール化合物の発見と合成

    日本薬学会第135年会  2015年 

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  • 新規分泌阻害剤の作用機序の解明

    第67回日本細胞生物学会大会  2015年 

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  • 新規ビスインドール化合物による分泌阻害の機序解明

    第34回日本糖質学会年会  2015年 

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  • 新規ビスインドール化合物がもつ分泌阻害活性の特徴付け

    第95春季年会(2015) 日本化学会  2015年 

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  • 酵母スクリーニング系を用いた benzyl isothiocyanate のがん予防機構解明

    日本農芸化学会2015  2015年 

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  • ナノカーボン複合樹脂材料におけるナノカーボンの分散性と機能との関連

    プラスチック成形加工学会  2015年 

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  • S-ニトロシル化laforinはlaforinの分解を阻害し、Lafora病に関連する

    第67回日本細胞生物学会大会  2015年 

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  • 糖タンパク質輸送に関与するERGIC-53の翻訳後修飾の機能解析

    2015年日本化学会中国四国支部大会  2015年 

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  • ルイス酸によって促進されるインドールへのC2位の付加反応の開発

    2015年日本化学会中国四国支部大会  2015年 

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  • Identification of benzyl isothiocyanate-targeted genes using a yeast screening system

    (ICoFF) International Conference on Food Factors  2015年 

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  • Lafora病における一酸化窒素の関与

    第38回日本分子生物学会年会・第88回日本生化学会大会 合同大会  2015年 

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  • S-ニトロシル化laforinのラフォラ病への関与

    2015年日本化学会中国四国支部大会  2015年 

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  • S-ニトロシル化ERGIC-53の特徴づけ

    第38回日本分子生物学会年会・第88回日本生化学会大会 合同大会  2015年 

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  • 悪性がんモデル動物の全身免疫能

    第38回日本分子生物学会年会・第88回日本生化学会大会 合同大会  2015年 

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  • Effects of a newly found active ingredient, Fraglide1, in Zhenjiang vinegar, on a model mouse of dietary obesity

    Pacifichem 2015  2015年 

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  • Identification of benzyl isothiocyanate-targeted genes using a yeast screening system

    Pacifichem 2015  2015年 

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  • Giantin regulates the early secretory pathway by controlling communication among Golgi stacks

    ISMB 2014  2014年 

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  • 一酸化窒素によるlaforinの化学修飾とLafora病への関与

    第66回日本細胞生物学会大会  2014年 

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  • 新規ビスインドール化合物がもつ分泌阻害活性の特徴付け

    第33回日本糖質学会年会  2014年 

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  • Giantin regulates the early secretory pathway by controlling communication among Golgi stacks

    第7回高度医療都市を創出する未来技術国際シンポジウム  2014年 

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  • Characterization of a novel bisindole containing compound in intracellular trafficking

    ISMB 2014  2014年 

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  • 一酸化窒素はLafora病に関与する

    第37回日本分子生物学会年会  2014年 

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  • p150Glued-interacting domains of TRAPPC9 reveal regulatory function of TRAPPC9 at the centrosome.

    第54回アメリカ細胞生物学会年会  2014年 

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  • High-throughput drug discovery of novel inhibitors of secretion

    第54回アメリカ細胞生物学会年会  2014年 

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  • リポフェクション試薬に代わる遺伝子導入試薬の探索

    第5回日本生物物理学会中国・四国支部会  2013年 

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  • The golgin tether Giantin regulates the secretory pathway by controlling stack organization within Golgi apparatus

    第65回日本細胞生物学会大会  2013年 

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  • ゴルジ体形成と分泌におけるゴルジンタンパク質の機能解析

    第32 回日本糖質学会年会  2013年 

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  • フルオロアルキルインドール類の合成と細胞死抑制活性評価

    2013年日本化学会中国四国支部大会  2013年 

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  • Giantin regulates the early secretory pathway by controlling communication among Golgi stacks

    第53回アメリカ細胞生物学会年会  2013年 

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  • CF3(トリフルオロメチル)基を含むインドール類の合成と細胞死抑制活性の評価

    第93春季年会(2013) 日本化学会  2013年 

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  • Development and characterization of cancer stem cell model from mouse iPS cells

    AACR Annual Meeting 2012  2012年 

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  • ニワトリASIP mRNAの各クラスがコードするタンパクの性格付け

    日本動物学会 第83回大会  2012年 

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  • マウス人工多能性幹細胞より誘導したがん幹細胞モデルの生体外解析

    第71回日本癌学会学術総会  2012年 

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  • Sec31のリン酸化と膜輸送におけるCK2の機能解析

    第35回日本分子生物学会年会  2012年 

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  • エボラウイルス表層糖タンパク質に対する糖鎖修飾制御メカニズムの解明

    第85回日本生化学会大会  2012年 

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  • The role of CK2 in Sec31 phosphorylation and membrane trafficking

    第52回アメリカ細胞生物学会年会  2012年 

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  • マウスiPSから作成したガン幹細胞モデルは顕著な血管新生を示す。

    第70回日本癌学会学術総会  2011年 

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  • Analysis of endothelium mimicry by the CSC-like cells derived from iPS cells

    第51回アメリカ細胞生物学会年会  2011年 

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  • Golginタンパク質群による糖転移酵素の輸送制御の解明

    GlycoTOKYO2011  2011年 

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  • Detection of in situ cleaved p115 in rapid protein inactivation

    第51回アメリカ細胞生物学会年会  2011年 

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  • 細胞内輸送による小胞体ストレス解消

    第6回小胞体ストレス研究会  2011年 

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  • ゴルジンタンパク質のゴルジ体形成における機能解析

    第33回生体膜と薬物の相互作用シンポジウム  2011年 

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  • ゴルジンタンパク質の機能解析ー小胞輸送とゴルジ体形成ー

    第84回日本生化学会大会  2011年 

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  • ゴルジンタンパク質、Giantinはゴルジ嚢の長さと輸送の調節に関係している

    第62回日本細胞生物学会大会  2010年 

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  • IPS細胞から作成したガン幹細胞モデル

    第69回日本癌学会学術総会  2010年 

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  • ゴルジ体や、細胞の大きさと輸送能力には相関があるか?

    第3回日本定量生物学会年会  2010年 

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  • The Goign tether, Giantin regulates Golgi size

    第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会  2010年 

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  • Analysis of ErbB2 internalization mechanism in SK-BR-3 cells

    第50回アメリカ細胞生物学会年会  2010年 

     詳細を見る

  • Loss-Of-Function of a Golgin Tether, Giantin Elongates Length of Golgi Cisternae Resulting Changes in Localization of Sugar Golgi Enzymes and Cargo Glycosylation

    第50回アメリカ細胞生物学会年会  2010年 

     詳細を見る

  • ゴルジンタンパク質、Giantinはゴルジ体における糖鎖修飾制御に関与する

    第29回日本糖質学会年会  2009年 

     詳細を見る

  • The role of phosphorylation of a COPII coat protein, Sec31 in molecular export from the endoplasmic reticulum

    第49回アメリカ細胞生物学会年会  2009年 

     詳細を見る

  • mTrs130 Is a Component of a Mammalian TRAPPii Complex, a Rab1 GEF That Binds to COPI Coated Vesicles.

    第49回アメリカ細胞生物学会年会  2009年 

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  • A Role for the Acidic Domain of the Golgin Tether p115 in Exocytic Transport

    第61回日本細胞生物学会大会  2009年 

     詳細を見る

  • The role of phosphorylation of a COPII coat protein, Sec31 in molecular export from the endoplasmic reticulum

    ゴードンリサーチカンファレンス2009  2009年 

     詳細を見る

  • ゴルジンタンパク質群のゴルジ体の形成への寄与

    佐藤あやの

    第44回日本分子生物学会年会   2021年12月1日 

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    開催年月日: 2021年12月1日 - 2021年12月3日

  • ゴルジ体の構造変化により糖鎖修飾は変化するのか? 招待

    佐藤あやの

    第40回日本糖質学会年会  2021年10月29日 

     詳細を見る

    開催年月日: 2021年10月27日 - 2021年10月29日

  • 複合型糖鎖を有するCholera Toxin B-Subunitの化学合成と生細胞への導入

    真木勇太、佐藤あやの、川田一希、岡本亮、梶原康宏

    第40回日本糖質学会年会  2021年10月28日 

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    開催年月日: 2021年10月27日 - 2021年10月29日

  • 化学的糖鎖挿入による糖タンパク質精密合成

    野村幸汰、真木勇太、岡本亮、佐藤あやの、梶原康宏

    第40回日本糖質学会年会  2021年10月27日 

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    開催年月日: 2021年10月27日 - 2021年10月29日

  • タンパク質糖鎖水和殻による水の動的挙動

    岡本 亮、真木 勇太、芝田 大之、 佐藤 あやの、樺山 一哉、梶原 康宏

    第40回日本糖質学会年会  2021年10月27日 

     詳細を見る

    開催年月日: 2021年10月27日 - 2021年10月29日

  • ゴルジンタンパク質、Giantin の欠失細胞におけるゴルジ体の三次元構造解析

    佐藤あやの

    第73回日本細胞生物学会大会  2021年6月30日 

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    開催年月日: 2021年6月29日 - 2021年7月2日

  • アトピー性皮膚炎惹起性の評価のための細胞アッセイの確立

    シンポジウム:細胞アッセイ技術の現状と将来  2021年1月26日 

  • Reporter Gene Expression in Heterosigma akashiwo which is a Causative Organism of the Harmful Algal Bloom

    Nanami Nakayama, Ayano Satoh, Shoko Ueki

    2020年12月16日 

  • Gene Manipulation Techniques in Heterosigma Akashiwo, a Causative Organism of Harmful Algal Blooms

    Nanami Nakayama, Shoko Ueki , Ayano Satoh

    2020年12月4日 

  • ゴルジ体の構造と糖鎖構造には関係があるのか?

    佐藤あやの

    第39回日本糖質学会年会  2020年11月23日 

  • 赤潮原因種Heterosigma akashiwoの遺伝子操作技術

    中山七海、植木尚子、佐藤あやの

    日本生物工学会西日本支部学会  2020年11月14日 

  • アトピー性皮膚炎惹起性評価のための試験法の確立

    加藤 浩介、辻野 義雄、佐藤 あやの

    日本生物工学会西日本支部学会  2020年11月14日 

  • アトピー性皮膚炎惹起性の評価のための動物実験代替法の確立

    加藤 浩介、辻野 義雄、佐藤 あやの

    日本動物実験代替法学会 第33回大会  2020年11月13日 

  • ゴルジンタンパク質である Giantin はゴルジ体ゾーンの形成に関与するか? 招待

    第72回日本細胞生物学会大会  2020年6月11日 

  • 赤潮原因藻ヘテロシグマのバイオテクノロジー的利用をめざした遺伝子導入法の検討

    第42回 日本分子生物学会年会  2019年12月6日 

  • コレラトキシンBサブユニットを利用した機能性ペプチドの細胞小器官への送達

    第71回日本生物工学会大会  2019年9月18日 

  • コレラトキシンBサブユニットを利用した機能性ペプチドの小胞体への特異的送達法の開発

    第38回日本糖質学会年会  2019年8月21日 

  • ゴルジ体ゾーンの形成にゴルジンタンパク質であるGiantinは関与するか 招待

    第19回日本蛋白質科学会年会 第71回日本細胞生物学会大会  2019年6月26日 

  • ゴルジンタンパク質であるGiantinはゴルジ体ゾーンの形成に関与するか?

    第41回日本分子生物学会年会   2018年11月30日 

  • Characterization of the novel inhibitor for protein secretion

    Ayano Satoh, Hideyuki Suzuki, Mitsuko Hayashi-Nishino, Kunihiko Nishino, Yuta Nishina

    2018年6月8日 

  • A 3D modeling of Golgi stacks in giantin knockdown cells

    Takuto Shakuno, Mitsuko Hayashi-Nishino, Kunihiko Nishino, Ayano Satoh

    2018年6月8日 

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産業財産権

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Works(作品等)

受賞

  • 保井コノ賞

    2021年2月  

     詳細を見る

  • 2020年度第2回「物質・デバイス共同研究賞」

    2020年6月   物質・デバイス領域共同研究拠点  

     詳細を見る

  • GLYCO2011 Tokyo

    2011年  

     詳細を見る

    受賞国:日本国

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共同研究・競争的資金等の研究

  • 糖タンパク質の革新的合成法の確立と翻訳後修飾の機能解明に向けたアプローチ

    研究課題/領域番号:21H04708  2021年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業 基盤研究(A)  基盤研究(A)

    梶原 康宏, 佐藤 あやの

      詳細を見る

    配分額:42510000円 ( 直接経費:32700000円 、 間接経費:9810000円 )

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  • 日本人特有の遺伝的背景が機能性食品成分の代謝・生理機能に与える影響

    研究課題/領域番号:20H02933  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    中村 宜督, 松本 明子, 増田 潤子, 佐藤 あやの, 中村 俊之

      詳細を見る

    配分額:18070000円 ( 直接経費:13900000円 、 間接経費:4170000円 )

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  • 低線量・低線量率放射線被ばくが疾病モデル動物の全身免疫能に及ぼす影響

    研究課題/領域番号:18K09780  2018年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    高山 英次, 佐藤 あやの, 一戸 辰夫, 本庶 仁子, 中田 隆博, 藤井 元, 徳野 慎一, 石塚 俊晶, 守本 祐司, 近藤 信夫, 神谷 真子, 川木 晴美, 梅村 直己

      詳細を見る

    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    広島大学原爆医科学研究所の動物飼育施設において、5週齢のマウスを購入して一週間馴化させ、7週齢で全身免疫能が増強される低線量の放射線被ばく後24時間以内に放射線障害治療を施し、全身免疫能、腫瘍の生着、および担がんマウスの生存日数を調べた。
    (4)放射線被ばく後の治療が全身免疫能に及ぼす影響:低線量の放射線被ばくのみのマウスに較べ、被ばく後の放射線障害治療で全身免疫能の増強がみられた。
    (5)放射線被ばく後の治療が腫瘍の生着に及ぼす影響:放射線被ばく後に腫瘍を移植した3週後に、低線量の放射線被ばくのみのマウスに較べ、被ばく後の放射線障害治療で腫瘍の生着に改善がみられた。
    (6)放射線被ばく後の治療が腫瘍の生着に及ぼす影響:放射線被ばく後に腫瘍を移植した7週後までで、低線量の放射線被ばくのみのマウスに較べ、被ばく後の放射線障害治療で生存率に改善がみられた。
    これまでの結果の再現性を確かめるとともに、研究成果の発表準備を進める。

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  • 新規分泌阻害剤の標的分子の探索によるゴルジ体維持と分泌に重要な因子の同定

    研究課題/領域番号:18K06133  2018年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    佐藤 あやの

      詳細を見る

    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

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  • 精密合成した糖タンパク質プローブを用いるゴルジ装置内糖鎖構造管理機構の解明

    研究課題/領域番号:17H01214  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業 基盤研究(A)  基盤研究(A)

    梶原 康宏, 佐藤 あやの

      詳細を見る

    配分額:39650000円 ( 直接経費:30500000円 、 間接経費:9150000円 )

    新規に確立した方法で合成した糖タンパク質をもちいて、水素重水素交換質量分析実験をおこない、糖鎖周辺の重水素化の交換速度が他のタンパク質表面と特異に違うことを見出した。また、化学合成し、かつフォールディングした糖タンパク質を生細胞のゴルジ体内に挿入することに成功した。糖タンパク質の糖鎖周辺のタンパク質表面を疎水性から親水性に変化させ、細胞培養するとN型糖鎖の分枝数の変化がおこることが明らかになった。遺伝子機能欠損によるゴルジ体の変化の構造の詳細を解析した。このゴルジ体の構造の変化によって細胞表面の糖鎖の構造が変化することを見出した。

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  • 酵母全遺伝子スクリーニングによる食品成分標的遺伝子の同定とその発現調節機構の解明

    研究課題/領域番号:17H03818  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    中村 宜督, 佐藤 あやの, 守屋 央朗, 中村 俊之

      詳細を見る

    配分額:17680000円 ( 直接経費:13600000円 、 間接経費:4080000円 )

    出芽酵母の遺伝子綱引き法(gTOW法)を用いた新たな評価モデル系を用いて、機能性食品成分ベンジルイソチオシアネート(BITC)の耐性遺伝子を探索し、酵母全6000遺伝子の中から12遺伝子を同定した。さらに、BITC耐性遺伝子の一つMTW1のヒトホモログ(Mis12)安定過剰発現ヒトがん細胞株を樹立し、これがBITCに対する高い抵抗性を示すこと、ノックダウンは逆に感受性が高まることを示した。また、Mis12はBITCにより翻訳後修飾を介して発現が下方調節され、細胞周期依存的にアポトーシスへの感受性を高めることによって、BITCの大腸がん細胞増殖抑制作用に貢献することが示唆された。

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  • 口腔扁平上皮癌モデル動物の抗腫瘍免疫能に低線量・低線量率放射線被ばくが及ぼす影響

    研究課題/領域番号:15K11096  2015年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    高山 英次, 一戸 辰夫, 佐藤 あやの, 増田 潤子, 近藤 信夫, 川木 晴美, 神谷 真子, 梅村 直己, 中田 隆博, 本庶 仁子, 足立 誠

      詳細を見る

    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    同系マウス腫瘍細胞株を皮下および静脈内に移植した、原発巣および肺転移巣モデルを確立した。骨髄球由来サプレッサー細胞(MDSC)は、原発巣モデルで増加した。CD4+およびCD8+T細胞およびCD4+Foxp3+T細胞は、原発巣モデルにおいて有意に減少した。さらに、原発巣モデルでTh1免疫能が増強した。原発巣モデルのTh1免疫能増強は、IL-4、IL-9およびIL-10産生能の減弱により特徴付けられた。肺転移巣モデルでは、IL-10産生が増強した。これらの結果は、腫瘍発生の様式が全身性免疫に異なる効果を及ぼし、癌患者の治療へのアプローチに影響を及ぼし得ることを示唆している。

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  • 細胞内輸送の高効率化とゴルジ体構造変化に関わるゴルジンタンパク質の機能解析

    研究課題/領域番号:26440055  2014年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    佐藤 あやの, 西野 邦彦, 西野 美都子, 仁科 勇太

      詳細を見る

    配分額:5070000円 ( 直接経費:3900000円 、 間接経費:1170000円 )

    これまでに、ゴルジンタンパク質群のひとつであるgiantinをノックダウンすると分泌が上がること、ゴルジ体の構造に変化が起こることを示した。本研究課題では、この現象に関わる分子機構を明らかにすることを最終的な目的とし、電子線トモグラフィーなどを用いゴルジ体の構造を詳細に解析した。また、この間、分泌調節に関わる新規小分子を発見したため、新規分子の特徴付けを合わせて行なった。本研究課題の期間は終了したが、引き続き、これらの解析や新規分子のターゲットの探索を行う予定である。

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  • ゴルジンタンパク質によるゴルジ嚢の長さ調節とカーゴ輸送調節の分子機構解明

    研究課題/領域番号:23570167  2011年 - 2013年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    佐藤 あやの

      詳細を見る

    配分額:5590000円 ( 直接経費:4300000円 、 間接経費:1290000円 )

    申請者は、分泌や輸送における中心的な役割を果たす細胞内小器官であるゴルジ体、とその周辺輸送に関わるゴルジンタンパク質群に関して研究を進めている。本研究では、ゴルジンファミリーに属する、Giantinが、細胞内の輸送とゴルジ体形成を調節するということを明らかにした。これらの事実は、Giantinの発現量を変化させることによって細胞内輸送や分泌を調節することができるということを意味する。つまり、Giantinを標的として、分泌調節薬の開発が可能であることを示唆する。

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担当授業科目

  • SDGs:生命科学 (2021年度) 第4学期  - 木7~8

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  • 化学生命系英語 (2020年度) 1・2学期  - 水3,水4

  • 化学生命系英語1 (2020年度) 第1学期  - 水3,水4

  • 化学生命系英語2 (2020年度) 第2学期  - 水3,水4

  • 専門英語 (2020年度) 3・4学期  - 木3,木4

  • 専門英語1 (2020年度) 第3学期  - 木3,木4

  • 専門英語2 (2020年度) 第4学期  - 木3,木4

  • 技術表現発表学 (2020年度) 後期  - その他

  • 教養生物学(バイオテクノロジー) (2020年度) 第4学期  - 木3,木4

  • 材料プロセス実験2 (2020年度) 第1学期  - 月4,月5,月6,月7,木4,木5,木6,木7

  • 材料プロセス実験2 (2020年度) 第1学期  - 月4,月5,月6,月7,木4,木5,木6,木7

  • 生命工学実験2 (2020年度) 第1学期  - 月4,月5,月6,月7,木4,木5,木6,木7

  • 生命工学実験3 (2020年度) 第3学期  - 火4,火5,火6,火7,金4,金5,金6,金7

  • 生命工学実験2 (2020年度) 第1学期  - 月4,月5,月6,月7,木4,木5,木6,木7

  • 生命工学実験3 (2020年度) 第3学期  - 火4,火5,火6,火7,金4,金5,金6,金7

▼全件表示