研究者詳細 - 佐藤　あやの

論文 - 佐藤　あやの

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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

The Journal of Immunology 186 ( 12 ) 6990 - 6998 2011年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：The American Association of Immunologists

Abstract

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-κB, 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.

DOI： 10.4049/jimmunol.1100396

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

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

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Society for Cell Biology (ASCB)

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 γ1COP, 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.

DOI： 10.1091/mbc.e09-05-0387

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

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

Traffic 10 ( 8 ) 994 - 1005 2009年7月

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

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

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 Fölsch, James M. Anderson, Zenta Walther, Ira Mellman

Traffic 9 ( 11 ) 1915 - 1924 2008年10月

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 syndecan‐1’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

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8月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

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

Ankyrin Repeat Proteins Comprise a Diverse Family of Bacterial Type IV Effectors 査読国際誌

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

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

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Association for the Advancement of Science (AAAS)

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.

DOI： 10.1126/science.1158160

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 103 ( 52 ) 19777 - 19782 2006年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Proceedings of the National Academy of 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.

DOI： 10.1073/pnas.0605907103

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

The Journal of Cell Biology 174 ( 3 ) 359 - 368 2006年7月

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 University 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.

DOI： 10.1083/jcb.200603044

A Cryptic Rab1-binding Site in the p115 TetheringProtein 査読国際誌

Matthew Beard, Ayano Satoh, James Shorter, Graham Warren

Journal of Biological Chemistry 280 ( 27 ) 25840 - 25848 2005年7月

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 BV

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.

DOI： 10.1074/jbc.m503925200

Golgin Tethers Define Subpopulations of COPI Vesicles 査読国際誌

Jörg Malsam, Ayano Satoh, Laurence Pelletier, Graham Warren

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

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Association for the Advancement of Science (AAAS)

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.

DOI： 10.1126/science.1108061

Mapping the Functional Domains of the Golgi Stacking Factor GRASP65 査読国際誌

Yanzhuang Wang, Ayano Satoh, Graham Warren

Journal of Biological Chemistry 280 ( 6 ) 4921 - 4928 2005年2月

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 BV

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.

DOI： 10.1074/jbc.m412407200

Tethering Assays for COPI Vesicles Mediated by Golgins 査読国際誌

Ayano Satoh, Jörg Malsam, Graham Warren

Methods in Enzymology 404 125 - 134 2005年

担当区分：筆頭著者記述言語：英語掲載種別：論文集(書籍)内論文出版者・発行元：Elsevier

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.

DOI： 10.1016/s0076-6879(05)04013-9

Preparation and Characterization of Recombinant Golgin Tethers 査読国際誌

Ayano Satoh, Matthew Beard, Graham Warren

Methods in Enzymology 404 279 - 296 2005年

担当区分：筆頭著者記述言語：英語掲載種別：論文集(書籍)内論文出版者・発行元：Elsevier

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.

DOI： 10.1016/s0076-6879(05)04026-7

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

Yanzhuang Wang, Ayano Satoh, Graham Warren, Hemmo H. Meyer

The Journal of Cell Biology 164 ( 7 ) 973 - 978 2004年3月

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 University 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

Golgin‐84 is a rab1 Binding Partner Involved in Golgi Structure 査読国際誌

Ayano Satoh, Yanzhuang Wang, Jörg Malsam, Matthew B. Beard, Graham Warren

Traffic 4 ( 3 ) 153 - 161 2003年3月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

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.

DOI： 10.1034/j.1600-0854.2003.00103.x

Fraglide-1 from traditional Chinese aromatic vinegar: A natural AhR antagonist for atopic dermatitis 国際誌

Kosuke Kato, Miki Akamatsu, Saya Kakimaru, Mayuko Koreishi, Masahiro Takagi, Masahiro Miyashita, Yoshiyuki Murata, Yoshimasa Nakamura, Ayano Satoh, Yoshio Tsujino

Food and Chemical Toxicology 197 115301 - 115301 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Traditional Chinese Zhenjiang aromatic vinegar (Kozu) contains Fraglide-1 (FG1), a bioactive lactone with demonstrated peroxisome proliferator-activated receptor gamma (PPARγ) agonist and antioxidant activities. This study explored FG1's novel ability to antagonize the aryl hydrocarbon receptor (AhR) signaling pathway, which regulates artemin expression and contributes to itching and inflammation in atopic dermatitis. Through molecular docking simulations and cell-based assays in human keratinocytes, we demonstrated FG1's potent antagonistic activity against AhR signaling. FG1 effectively suppressed FICZ-induced inflammatory responses, including artemin expression, with potency (half maximal inhibitory concentration, IC50 = 5.1 μM) comparable to the synthetic antagonist StemRegenin 1 (SR1) while demonstrating a superior safety profile (median lethal concentration, LC50 > 100 μM vs. 27.5 μM for SR1). These findings expand our understanding of bioactive compounds from traditional fermented foods and their regulatory effects on AhR signaling, providing a foundation for future studies on FG1's role in modulating skin inflammation.

DOI： 10.1016/j.fct.2025.115301

Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways

Saki Okamoto, Saya Kakimaru, Mayuko Koreishi, Mika Sakamoto, Yoshimasa Nakamura, Hideya Ando, Yoshio Tsujino, Ayano Satoh

Journal of Functional Foods 2025年2月

PTPA localized in the Golgi apparatus plays an important role in osteoblast differentiation.

Zheng X, Weng Y, Satoh A, Tanai A, Ikegame M, Kimura K, Yoshitani N, Xie X, Okamura H

Biochemical and biophysical research communications 748 151329 - 151329 2025年1月

掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

Regulatory subunits of protein phosphatase 2A (PP2A) define the substrate and functional specificity of the PP2A holoenzyme within specific organelles. While PP2A regulates osteoblast differentiation, the roles and localization of its regulatory subunits in osteoblasts remain unclear. Here, we identified PTPA, a PP2A regulatory protein, predominantly localized to the Golgi apparatus, closely overlapping with the Golgi marker Giantin. Disruption of the Golgi structure by Brefeldin A caused PTPA to disperse into the cytoplasm. PTPA overexpression inhibited osteoblast differentiation by downregulating key transcriptional regulators. The Golgi-specific localization of PTPA suggests it may influence bone-related protein secretion and maintain Golgi integrity. These findings highlight the critical role of PTPA in osteoblast differentiation and its association with the Golgi apparatus.

DOI： 10.1016/j.bbrc.2025.151329

Evaluation of quercetin as a potential cytoprotector against acetaldehyde using the cultured hepatocyte model with aldehyde dehydrogenase isozyme deficiency. 査読国際誌

Yuhang Xu, Takeshi Sawamoto, Ruitong Sun, Aki Ishikura, Shintaro Munemasa, Yoshiyuki Murata, Ayano Satoh, Akiko Matsumoto, Toshiyuki Nakamura, Yoshimasa Nakamura

Bioscience, biotechnology, and biochemistry 88 ( 10 ) 1199 - 1202 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Protective effect of quercetin against acetaldehyde was evaluated using the cultured hepatocyte models with aldehyde dehydrogenase (ALDH) isozyme deficiency (aldh2-kd and aldh1a1-kd). The quercetin-induced cytoprotection against acetaldehyde in the ALDH1A1-deficient mutant (aldh1a1-kd) was weaker than that in the wild type. Furthermore, quercetin did not enhance the ALDH activity in aldh1a1-kd cells, suggesting that ALDH1A1 is involved in quercetin-induced cytoprotection.

DOI： 10.1093/bbb/zbae100

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