Updated on 2025/10/23

写真a

 
OMOTE Hiroshi
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Associate Professor
Position
Associate Professor
Profile

膜輸送体の生理、生化学に取り組んでいます。
特に神経伝達に関わる小胞型トランスポーターや薬物排泄トランスポーターの輸送機構や生理的役割を解析しています。トランスポーターの世界は未知のものも多く、また既に知られているトランスポーターであっても知られていない機能を持っているものがあります。このような知られざる機能を明らかにしていきたいと考えています。

 

生体膜生理化学研究室

External link

Degree

  • Ph.D. ( 1993.3   Osaka University )

Research Interests

  • glucose transporter

  • polyamine transporter

  • P-糖タンパク質

  • ATP合成酵素

  • グルタミン酸輸送体

  • chemical transmission

  • drug export

  • transporter

  • VitaminC

  • nucleotide transporter

  • ポリアミン

Research Areas

  • Life Science / Pharmaceutical hygiene and biochemistry

  • Life Science / Neuroscience-general

  • Life Science / Functional biochemistry

Education

  • Osaka University   大学院理学研究科   生物化学専攻 博士後期課程

    1990.4 - 1993.3

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  • Shizuoka University   大学院理学研究科   生物学専攻 修士課程

    1988.4 - 1990.3

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  • Shinshu University   理学部   生物学科

    1983.4 - 1987.3

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Research History

  • Medicine, Dentistry and Pharmaceutical Sciences, Okayama University   Membrane Biochemistry & Biophysiology   Associate Professor

    2021.4

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    Country:Japan

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  • Okayama University   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences   Associate Professor

    2007.4

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  • Okayama University   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences   Associate Professor (as old post name)

    2005.4 - 2007.3

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  • Okayama University   The Graduate School of Natural Science and Technology   Associate Professor (as old post name)

    2004.4 - 2005.3

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  • 米国バージニア大学   リサーチアソシエイト

    1999.4 - 2004.3

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  • Osaka University   The Institute of Scientific and Industrial Research   Research Assistant

    1995.1 - 2001.3

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  • Osaka University   The Institute of Scientific and Industrial Research   Special researcher of the Japan Society for the Promotion of Science

    1993.4 - 1994.12

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Professional Memberships

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Papers

  • Polyamine release and vesicular polyamine transporter expression in megakaryoblastic cells and platelets. Reviewed International journal

    Mizuki Uehara, Ayaka Fukumoto, Hiroshi Omote, Miki Hiasa

    Biochimica et biophysica acta. General subjects   1868 ( 6 )   130610 - 130610   2024.6

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Polyamines not only play essential roles in cell growth and function of living organisms but are also released into the extracellular space and function as regulators of chemical transduction, although the cells from which they are released and their mode of release are not well understood. The vesicular polyamine transporter (VPAT), encoded by the SLC18B1 is responsible for the vesicular storage of spermine and spermidine, followed by their vesicular release from secretory cells. Focusing on VPAT will help identify polyamine-secreting cells and new polyamine functions. In this study, we investigated the possible involvement of VPAT in vesicular release of polyamines in MEG-01 clonal megakaryoblastic cells and platelets. RT-PCR, western blotting, and immunohistochemistry revealed VPAT expression in MEG-01 cells. MEG-01 cells secreted polyamines upon A23187 stimulation in the presence of Ca2+, which is temperature-dependent and sensitive to bafilomycin A1. A23187-induced polyamine secretion from MEG-01 cells was reduced by treatment with reserpine, VPAT inhibitors, or VPAT RNA interference. Platelets also expressed VPAT, displaying a punctate distribution, and released spermidine upon A23187 and thrombin stimulation. These findings have demonstrated VPAT-mediated vesicular polyamine release from MEG-01 cells, suggesting the presence of similar vesicular polyamine release mechanisms in platelets.

    DOI: 10.1016/j.bbagen.2024.130610

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  • Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors Reviewed

    Loc Dinh Hoang, Eriko Aoyama, Miki Hiasa, Hiroshi Omote, Satoshi Kubota, Takuo Kuboki, Masaharu Takigawa

    International Journal of Molecular Sciences   24 ( 24 )   17294 - 17294   2023.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

    DOI: 10.3390/ijms242417294

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  • Functional characterization and tissue localization of the facilitative glucose transporter GLUT12 Reviewed

    Shunsuke Matsuo, Miki Hiasa, Hiroshi Omote

    The Journal of Biochemistry   168 ( 6 )   611 - 620   2020.12

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    <title>Abstract</title>Facilitative glucose transporters (GLUTs) play crucial roles in glucose utilization and homeostasis. GLUT12 was initially isolated as a novel GLUT4-like transporter involved in insulin-dependent glucose transport. However, tissue distribution and biochemical properties of GLUT12 are not well understood. In this study, we investigated the basic kinetic properties and tissue distribution of GLUT12. Human GLUT12 and GLUT1 were overexpressed and purified using Ni-NTA column chromatography. Reconstituted proteoliposomes showed time-dependent d-glucose transport activity, which was inhibited by phloretin and dehydroascorbate. Dose dependence of glucose transport revealed a KM and Vmax values of 6.4 mM and 1.2 μmol/mg/min, respectively, indicating that GLUT12 is a high-affinity type GLUT. Glucose transport by GLUT12 was inhibited by ATP and glucose-1-phosphate, glucose-6-phosphate and disaccharides (properties similar to those of GLUT1). Indirect immunohistochemistry revealed the distribution of mouse GLUT12 in the apical region of distal tubules and collecting ducts in the kidney and epithelial cells of the jejunum. In addition to these cells, GLUT12 was present in chromaffin cells in the adrenal medulla, the anterior pituitary lobe, as well as the thyroid and pyloric glands. These tissue distributions suggest a unique function of GLUT12, besides that of an insulin-dependent glucose transport.

    DOI: 10.1093/jb/mvaa090

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    Other Link: http://academic.oup.com/jb/article-pdf/168/6/611/35149301/mvaa090.pdf

  • The mitochondrial inner membrane protein LETM1 modulates cristae organization through its LETM domain. Reviewed International journal

    Seiko Nakamura, Aiko Matsui, Shiori Akabane, Yasushi Tamura, Azumi Hatano, Yuriko Miyano, Hiroshi Omote, Mizuho Kajikawa, Katsumi Maenaka, Yoshinori Moriyama, Toshiya Endo, Toshihiko Oka

    Communications biology   3 ( 1 )   99 - 99   2020.3

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    LETM1 is a mitochondrial inner membrane protein that is required for maintaining the mitochondrial morphology and cristae structures, and regulates mitochondrial ion homeostasis. Here we report a role of LETM1 in the organization of cristae structures. We identified four amino acid residues of human LETM1 that are crucial for complementation of the growth deficiency caused by gene deletion of a yeast LETM1 orthologue. Substituting amino acid residues with alanine disrupts the correct assembly of a protein complex containing LETM1 and prevents changes in the mitochondrial morphology induced by exogenous LETM1 expression. Moreover, the LETM1 protein changes the shapes of the membranes of in vitro-reconstituted proteoliposomes, leading to the formation of invaginated membrane structures on artificial liposomes. LETM1 mutant proteins with alanine substitutions fail to facilitate the formation of invaginated membrane structures, suggesting that LETM1 plays a fundamental role in the organization of mitochondrial membrane morphology.

    DOI: 10.1038/s42003-020-0832-5

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  • Function of essential chloride and arginine residue in nucleotide binding to vesicular nucleotide transporter. Reviewed International journal

    Iwai Y, Kamatani S, Moriyama S, Omote H

    Journal of biochemistry   165 ( 6 )   479 - 486   2019.6

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    Vesicular nucleotide transporter (VNUT) plays a key role in purinergic signalling through its ability to transport nucleotides. VNUT belongs to the SLC17 family, which includes vesicular glutamate transporters (VGLUTs) and Type I Na+/phosphate cotransporters. All of these transporters exhibit membrane potential and Cl--dependent organic anion transport activity and have essential arginine in the transmembrane region. Previously, we reported that ketoacids inhibit these transporters through modulation of Cl- activation. Although this regulation is important to control signal transmission, the mechanisms underlying Cl--dependent regulation are unclear. Here, we examined the functional roles of Cl- and essential arginine residue on ATP binding to VNUT using the fluorescent ATP analogue trinitrophenyl-ATP (TNP-ATP). The fluorescence of TNP-ATP was enhanced by VNUT, whereas no enhancement was observed by VGLUT. Concentration-dependence curves showed that TNP-ATP was a high-affinity fluorescent probe for VNUT, with a Kd of 4.8 μM. TNP-ATP binding was competitive to ATP and showed similar specificity to transport activity. Addition of Cl- and ketoacids did not affect the apparent affinity for TNP-ATP. The Arg119 to Ala mutant retained TNP-ATP binding ability with slightly reduced affinity. Overall, these results indicated that Cl- and essential arginine were not important for ATP binding.

    DOI: 10.1093/jb/mvz002

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  • Purification and reconstitution of polyspecific H+/organic cation antiporter human MATE1. Reviewed International journal

    Kawasaki T, Matsumoto T, Iwai Y, Kawakami M, Juge N, Omote H, Nabekura T, Moriyama Y

    Biochimica et biophysica acta. Biomembranes   1860 ( 11 )   2456 - 2464   2018.11

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    Human MATE1 (multidrug and toxin extrusion 1, hMATE1) is a H+/organic cation (OC) exchanger responsible for the final step of toxic organic cation excretion in the kidney and liver. To investigate the mechanism of transport, we have established an in vitro assay procedure that includes its expression in insect cells, solubilization with octyl glucoside, purification, and reconstitution into liposomes. The resultant proteoliposomes containing hMATE1 as the sole protein component took up radiolabeled tetraethylammonium (TEA) in a ∆pH-dependent and electroneutral fashion. Furthermore, lipid-detergent micelle containing hMATE1 showed ∆pH-dependent TEA binding similar to transport. Mutated hMATE1 with replacement E273Q completely lacked these TEA binding and transport. In the case of divalent substrates, transport was electrogenic. These observations indicate that the stoichiometry of OC/H+ exchange is independent of substrate charge. Purification and reconstitution of hMATE1 is considered to be suitable for understanding the detailed molecular mechanisms of hMATE1. The results suggest that Glu273 of hMATE1 plays essential roles in substrate binding and transport.

    DOI: 10.1016/j.bbamem.2018.07.005

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  • Outward open conformation of a Major Facilitator Superfamily multidrug/H+ antiporter provides insights into switching mechanism. Reviewed International journal

    Nagarathinam K, Nakada-Nakura Y, Parthier C, Terada T, Juge N, Jaenecke F, Liu K, Hotta Y, Miyaji T, Omote H, Iwata S, Nomura N, Stubbs MT, Tanabe M

    Nature communications   9 ( 1 )   4005 - 4005   2018.10

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    Multidrug resistance (MDR) poses a major challenge to medicine. A principle cause of MDR is through active efflux by MDR transporters situated in the bacterial membrane. Here we present the crystal structure of the major facilitator superfamily (MFS) drug/H+ antiporter MdfA from Escherichia coli in an outward open conformation. Comparison with the inward facing (drug binding) state shows that, in addition to the expected change in relative orientations of the N- and C-terminal lobes of the antiporter, the conformation of TM5 is kinked and twisted. In vitro reconstitution experiments demonstrate the importance of selected residues for transport and molecular dynamics simulations are used to gain insights into antiporter switching. With the availability of structures of alternative conformational states, we anticipate that MdfA will serve as a model system for understanding drug efflux in MFS MDR antiporters.

    DOI: 10.1038/s41467-018-06306-x

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  • Efficient Mass Spectral Analysis of Active Transporters Overexpressed in Escherichia coli Reviewed

    Mamiyo Kawakami, Narinobu Juge, Yuri Kato, Hiroshi Omote, Yoshinori Moriyama, Takaaki Miyaji

    Journal of Proteome Research   17 ( 3 )   1108 - 1119   2018.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Chemical Society  

    DOI: 10.1021/acs.jproteome.7b00777

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  • Reconstitution and transport analysis of eukaryotic transporters in the post-genomic era Reviewed

    Hiroshi Omote, Yoshinori Moriyama

    Methods in Molecular Biology   1700   343 - 352   2018

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Part of collection (book)   Publisher:Humana Press Inc.  

    DOI: 10.1007/978-1-4939-7454-2_19

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  • Vesicular nucleotide transporter mediates ATP release and migration in neutrophils Reviewed

    Yuika Harada, Yuri Kato, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa

    Journal of Biological Chemistry   293 ( 10 )   3770 - 3779   2018

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Society for Biochemistry and Molecular Biology Inc.  

    DOI: 10.1074/jbc.M117.810168

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  • Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling Reviewed

    Yoshinori Moriyama, Miki Hiasa, Shohei Sakamoto, Hiroshi Omote, Masatoshi Nomura

    PURINERGIC SIGNALLING   13 ( 3 )   387 - 404   2017.9

  • Identification of a vesicular ATP release inhibitor for the treatment of neuropathic and inflammatory pain Reviewed

    Yuri Kato, Miki Hiasa, Reiko Ichikawa, Nao Hasuzawa, Atsushi Kadowaki, Ken Iwatsuki, Kazuhiro Shima, Yasuo Endo, Yoshiro Kitahara, Tsuyoshi Inoue, Masatoshi Nomura, Hiroshi Omote, Yoshinori Moriyama, Takaaki Miyaji

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   114 ( 31 )   E6297 - E6305   2017.8

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    DOI: 10.1073/pnas.1704847114

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  • Function and expression of a splicing variant of vesicular glutamate transporter 1 Reviewed

    Satomi Moriyama, Masafumi Iharada, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa

    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES   1859 ( 5 )   931 - 940   2017.5

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    DOI: 10.1016/j.bbamem.2017.02.002

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  • Vesicular Polyamine Transporter Mediates Vesicular Storage and Release of Polyamine from Mast Cells Reviewed

    Tomoya Takeuchi, Yuika Harada, Satomi Moriyama, Kazuyuki Furuta, Satoshi Tanaka, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa

    JOURNAL OF BIOLOGICAL CHEMISTRY   292 ( 9 )   3909 - 3918   2017.3

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    DOI: 10.1074/jbc.M116.756197

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  • Structure, Function, and Drug Interactions of Neurotransmitter Transporters in the Postgenomic Era Reviewed

    Hiroshi Omote, Takaaki Miyaji, Miki Hiasa, Narinobu Juge, Yoshinori Moriyama

    ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 56   56   385 - 402   2016

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    DOI: 10.1146/annurev-pharmtox-010814-124816

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  • Wide expression of type I Na+-phosphate cotransporter 3 (NPT3/SLC17A2), a membrane potential-driven organic anion transporter Reviewed

    Natsuko Togawa, Narinobu Juge, Takaaki Miyaji, Miki Hiasa, Hiroshi Omote, Yoshinori Moriyama

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   309 ( 2 )   C71 - C80   2015.7

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    DOI: 10.1152/ajpcell.00048.2015

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  • Plasmodium falciparum chloroquine resistance transporter is a H+-coupled polyspecific nutrient and drug exporter Reviewed

    Narinobu Juge, Sawako Moriyama, Takaaki Miyaji, Mamiyo Kawakami, Haruka Iwai, Tomoya Fukui, Nathan Nelson, Hiroshi Omote, Yoshinori Moriyama

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   112 ( 11 )   3356 - 3361   2015.3

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    DOI: 10.1073/pnas.1417102112

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  • AtPHT4;4 is a chloroplast-localized ascorbate transporter in Arabidopsis Reviewed

    Takaaki Miyaji, Takashi Kuromori, Yu Takeuchi, Naoki Yamaji, Kengo Yokosho, Atsushi Shimazawa, Eriko Sugimoto, Hiroshi Omote, Jian Feng Ma, Kazuo Shinozaki, Yoshinori Moriyama

    NATURE COMMUNICATIONS   6   5928   2015.1

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    DOI: 10.1038/ncomms6928

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  • NPT homologue (SLC17A4) is an intestinal urate exporter

    Natsuko Togawa, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama

    PURINERGIC SIGNALLING   10 ( 4 )   789 - 789   2014.12

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  • Identification of a mammalian vesicular polyamine transporter Reviewed

    Miki Hiasa, Takaaki Miyaji, Yuka Haruna, Tomoya Takeuchi, Yuika Harada, Sawako Moriyama, Akitsugu Yamamoto, Hiroshi Omote, Yoshinori Moriyama

    SCIENTIFIC REPORTS   4   6836   2014.10

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    DOI: 10.1038/srep06836

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  • Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity Reviewed

    Shohei Sakamoto, Takaaki Miyaji, Miki Hiasa, Reiko Ichikawa, Akira Uematsu, Ken Iwatsuki, Atsushi Shibata, Hisayuki Uneyama, Ryoichi Takayanagi, Akitsugu Yamamoto, Hiroshi Omote, Masatoshi Nomura, Yoshinori Moriyama

    SCIENTIFIC REPORTS   4   6689   2014.10

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    DOI: 10.1038/srep06689

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  • Involvement of the Leaf-Specific Multidrug and Toxic Compound Extrusion (MATE) Transporter Nt-JAT2 in Vacuolar Sequestration of Nicotine in Nicotiana tabacum Reviewed

    Nobukazu Shitan, Shota Minami, Masahiko Morita, Minaho Hayashida, Shingo Ito, Kojiro Takanashi, Hiroshi Omote, Yoshinori Moriyama, Akifumi Sugiyama, Alain Goossens, Masataka Moriyasu, Kazufumi Yazaki

    PLOS ONE   9 ( 9 )   e108789   2014.9

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    DOI: 10.1371/journal.pone.0108789

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  • Components of Foods Inhibit a Drug Exporter, Human Multidrug and Toxin Extrusion Transporter 1 Reviewed

    Tatsuya Kawasaki, Hideyuki Ito, Hiroshi Omote

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   37 ( 2 )   292 - 297   2014.2

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    DOI: 10.1248/bpb.b13-00815

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  • Essential role of vesicular nucleotide transporter in vesicular storage and release of nucleotides in platelets Reviewed

    Miki Hiasa, Natsuko Togawa, Takaaki Miyaji, Hiroshi Omote, Akitsugu Yamamoto, Yoshinori Moriyama

    Physiological Reports   2 ( 6 )   2014

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    DOI: 10.14814/phy2.12034

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  • Vesicular GABA transporter (VGAT) transports β-alanine Reviewed

    Narinobu Juge, Hiroshi Omote, Yoshinori Moriyama

    Journal of Neurochemistry   127 ( 4 )   482 - 486   2013.11

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    DOI: 10.1111/jnc.12393

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  • Inhibitors of ATP release inhibit vesicular nucleotide transporter Reviewed

    Yuri Kato, Hiroshi Omote, Takaaki Miyaji

    Biological and Pharmaceutical Bulletin   36 ( 11 )   1688 - 1691   2013.11

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    DOI: 10.1248/bpb.b13-00544

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  • Vesicular neurotransmitter transporters: An approach for studying transporters with purified proteins Reviewed

    Hiroshi Omote, Yoshinori Moriyama

    Physiology   28 ( 1 )   39 - 50   2013.1

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    DOI: 10.1152/physiol.00033.2012

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  • Type 1 sodium-dependent phosphate transporter acts as a membrane potential-driven urate exporter Reviewed

    Takaaki Miyaji, Tatsuya Kawasaki, Natsuko Togawa, Hiroshi Omote, Yoshinori Moriyama

    Current Molecular Pharmacology   6 ( 2 )   88 - 94   2013

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    DOI: 10.2174/18744672113069990035

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  • A Na+-phosphate cotransporter homologue (SLC17A4 protein) is an intestinal organic anion exporter Reviewed

    Natsuko Togawa, Takaaki Miyaji, Sho Izawa, Hiroshi Omote, Yoshinori Moriyama

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   302 ( 11 )   C1652 - C1660   2012.6

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    DOI: 10.1152/ajpcell.00015.2012

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  • Divalent Cation Transport by Vesicular Nucleotide Transporter Reviewed

    Takaaki Miyaji, Keisuke Sawada, Hiroshi Omote, Yoshinori Moriyama

    JOURNAL OF BIOLOGICAL CHEMISTRY   286 ( 50 )   42881 - 42887   2011.12

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    DOI: 10.1074/jbc.M111.277269

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  • Functional characterization of vesicular excitatory amino acid transport by human sialin Reviewed

    Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama

    JOURNAL OF NEUROCHEMISTRY   119 ( 1 )   1 - 5   2011.10

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    DOI: 10.1111/j.1471-4159.2011.07388.x

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  • Characterization of the human MATE2 proton-coupled polyspecific organic cation exporter Reviewed

    Toshinori Komatsu, Miki Hiasa, Takaaki Miyaji, Takuji Kanamoto, Takuya Matsumoto, Masato Otsuka, Yoshinori Moriyama, Hiroshi Omote

    INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY   43 ( 6 )   913 - 918   2011.6

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    DOI: 10.1016/j.biocel.2011.03.005

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  • Vesicular Neurotransmitter Transporter: Bioenergetics and Regulation of Glutamate Transport Reviewed

    Hiroshi Omote, Takaaki Miyaji, Narinobu Juge, Yoshinori Moriyama

    BIOCHEMISTRY   50 ( 25 )   5558 - 5565   2011.6

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    DOI: 10.1021/bi200567k

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  • A Vesicular Transporter That Mediates Aspartate and Glutamate Neurotransmission Reviewed

    Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   33 ( 11 )   1783 - 1785   2010.11

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    DOI: 10.1248/bpb.33.1783

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  • Metabolic Control of Vesicular Glutamate Transport and Release Reviewed

    Narinobu Juge, John A. Gray, Hiroshi Omote, Takaaki Miyaji, Tsuyoshi Inoue, Chiaki Hara, Hisayuki Uneyama, Robert H. Edwards, Roger A. Nicoll, Yoshinori Moriyama

    NEURON   68 ( 1 )   99 - 112   2010.10

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    DOI: 10.1016/j.neuron.2010.09.002

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  • Type 1 Sodium-dependent Phosphate Transporter (SLC17A1 Protein) Is a Cl--dependent Urate Exporter Reviewed

    Masafumi Iharada, Takaaki Miyaji, Takahiro Fujimoto, Miki Hiasa, Naohiko Anzai, Hiroshi Omote, Yoshinori Moriyama

    JOURNAL OF BIOLOGICAL CHEMISTRY   285 ( 34 )   26107 - 26113   2010.8

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    DOI: 10.1074/jbc.M110.122721

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  • Tricks of the trade used to accelerate high-resolution structure determination of membrane proteins Reviewed

    Yo Sonoda, Alex Cameron, Simon Newstead, Hiroshi Omote, Yoshinori Moriyama, Michihiro Kasahara, So Iwata, David Drew

    FEBS LETTERS   584 ( 12 )   2539 - 2547   2010.6

  • Vesicular Inhibitory Amino Acid Transporter Is a Cl-/gamma-Aminobutyrate Co-transporter Reviewed

    Narinobu Juge, Akiko Muroyama, Miki Hiasa, Hiroshi Omote, Yoshinori Moriyama

    JOURNAL OF BIOLOGICAL CHEMISTRY   284 ( 50 )   35073 - 35078   2009.12

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  • Vesicular glutamate transporter acts as a metabolic regulator Reviewed

    Yoshinori Moriyama, Hiroshi Omote

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   31 ( 10 )   1844 - 1846   2008.10

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    DOI: 10.1248/bpb.31.1844

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  • Identification of a vesicular aspartate transporter Reviewed

    Takaaki Miyaji, Noriko Echigo, Miki Hiasa, Shigenori Senoh, Hiroshi Omote, Yoshinori Moriyama

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   105 ( 33 )   11720 - 11724   2008.8

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    DOI: 10.1073/pnas.0804015105

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  • Identification of a vesicular nucleotide transporter Reviewed

    Keisuke Sawada, Noriko Echigo, Narinobu Juge, Takaaki Miyaji, Masato Otsuka, Hiroshi Omote, Akitsugu Yamamoto, Yoshinori Moriyama

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   105 ( 15 )   5683 - 5686   2008.4

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    DOI: 10.1073/pnas.0800141105

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  • Role of glutamate residues in substrate recognition by human MATE1 polyspecific H+/organic cation exporter Reviewed

    Takuya Matsumoto, Takuji Kanamoto, Masato Otsuka, Hiroshi Omote, Yoshinori Moriyama

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   294 ( 4 )   C1074 - C1078   2008.4

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    DOI: 10.1152/ajpcell.00504.2007

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  • A novel variant of mouse MATE-1 H+/organic cation antiporter with a long hydrophobic tall Reviewed

    Ayumi Kobara, Miki Hiasa, Takuya Matsumoto, Masato Otsuka, Hiroshi Omote, Yoshinori Moriyama

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   469 ( 2 )   195 - 199   2008.1

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    DOI: 10.1016/j.abb.2007.10.010

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  • [Identification, structure and function of a drug transporter at the final step of extrusion]. Reviewed

    Hiasa M, Omote H, Moriyama Y

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   53 ( 1 )   52 - 58   2008.1

  • Multidrug and toxic compound extrusion (MATE)-type proteins as anchor transporters for the excretion of metabolic waste products and xenobiotics Reviewed

    Y. Moriyama, M. Hiasa, T. Matsumoto, H. Omote

    XENOBIOTICA   38 ( 7-8 )   1107 - 1118   2008

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    DOI: 10.1080/00498250701883753

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  • Functional characterization of testis-specific rodent multidrug and toxic compound extrusion 2, a class III MATE-type polyspecific H+/organic cation exporter Reviewed

    Miki Hiasa, Takuya Matsumoto, Toshinori Komatsu, Hiroshi Omote, Yoshinori Moriyama

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   293 ( 5 )   C1437 - C1444   2007.11

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    DOI: 10.1152/ajpcell.00280.2007

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  • Molecular mechanism of vesicular glutamate transporter Reviewed

    Hiroshi Omote, Narinobu Juge

    SEIKAGAKU   79 ( 10 )   956 - 960   2007.10

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  • Vesicular glutamate transporter contains two independent transport machineries Reviewed

    Narinobu Juge, Yumi Yoshida, Shouki Yatsushiro, Hiroshi Omote, Yoshinori Moriyama

    JOURNAL OF BIOLOGICAL CHEMISTRY   281 ( 51 )   39499 - 39506   2006.12

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    DOI: 10.1074/jbc.M607670200

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  • The MATE proteins as fundamental transporters of metabolic and xenobiotic organic cations Reviewed

    Hiroshi Omote, Miki Hiasa, Takuya Matsumoto, Masato Otsuka, Yoshinori Moriyama

    TRENDS IN PHARMACOLOGICAL SCIENCES   27 ( 11 )   587 - 593   2006.11

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    DOI: 10.1016/j.tips.2006.09.001

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  • Secretion of L-glutamate from osteoclasts through transcytosis Reviewed

    Riyo Morimoto, Shunsuke Uehara, Shouki Yatsushiro, Narinobu Juge, Zhaolin Hua, Shigenori Senoh, Noriko Echigo, Mitsuko Hayashi, Toshihide Mizoguchi, Tadashi Ninomiya, Nobuyuki Udagawa, Hiroshi Omote, Akitsugu Yamamoto, Robert H. Edwards, Yoshinori Moriyama

    EMBO JOURNAL   25 ( 18 )   4175 - 4186   2006.9

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    DOI: 10.1038/sj.emboj.7601317

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  • 破骨細胞によるトランスサイトーシスを介したグルタミン酸分泌とその生理的意義

    上原 俊介, 森本 理代, 八代 聖基, 樹下 成信, 林 美都子, 妹尾 繁範, 溝口 利英, 二宮 禎, 宇田川 信之, Hua Zhaolin, 表 弘志, 山本 章嗣, Edwards Robert H., 森山 芳則

    松本歯学   32 ( 2 )   171 - 172   2006.8

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  • Interaction of transported drugs with the lipid bilayer and beta-glycoprotein through a solvation exchange mechanism Reviewed

    H Omote, MK Al-Shawi

    BIOPHYSICAL JOURNAL   90 ( 11 )   4046 - 4059   2006.6

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    DOI: 10.1529/biophysj.105.077743

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  • Examination of drug resistance activity of human TAP-like (ABCB9) expressed in yeast Reviewed

    A Ohashi-Kobayashi, K Ohashi, WB Du, H Omote, R Nakamoto, M Al-shawi, M Maeda

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   343 ( 2 )   597 - 601   2006.5

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    DOI: 10.1016/j.bbrc.2006.03.002

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  • Transmembrane topology of vesicular glutamate transporter 2 Reviewed

    SK Jung, R Morimoto, M Otsuka, H Omote

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   29 ( 3 )   547 - 549   2006.3

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    DOI: 10.1248/bpb.29.547

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  • A human transporter protein that mediates the final excretion step for toxic organic cations Reviewed

    M Otsuka, T Matsumoto, R Morimoto, S Arioka, H Omote, Y Moriyama

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   102 ( 50 )   17923 - 17928   2005.12

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    DOI: 10.1073/pnas.0506483102

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  • The remarkable transport mechanism of P-glycoprotein: A multidrug transporter Reviewed

    MK Al-Shawi, H Omote

    JOURNAL OF BIOENERGETICS AND BIOMEMBRANES   37 ( 6 )   489 - 496   2005.12

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    DOI: 10.1007/s10863-005-9497-5

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  • Proteolipid of vacuolar H+-ATPase of Plasmodium falciparum: cDNA cloning, gene organization and complementation of a yeast null mutant Reviewed

    Shouki Yatsushiro, Shinya Taniguchi, Toshihide Mitamura, Hiroshi Omote, Yoshinori Moriyama

    Biochimica et Biophysica Acta - Biomembranes   1717 ( 2 )   89 - 96   2005.11

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    DOI: 10.1016/j.bbamem.2005.08.011

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  • Identification of essential amino acid residues of the NorM Na+/multidrug antiporter in Vibrio parahaemolyticus Reviewed

    M Otsuka, M Yasuda, Y Morita, C Otsuka, T Tsuchiya, H Omote, Y Moriyama

    JOURNAL OF BACTERIOLOGY   187 ( 5 )   1552 - 1558   2005.3

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    DOI: 10.1128/jb.187.1552-1558.2005

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  • Improved energy coupling of human P-glycoprotein by the glycine 185 to valine mutation Reviewed

    H Omote, RA Figler, MK Polar, MK Al-Shawi

    BIOCHEMISTRY   43 ( 13 )   3917 - 3928   2004.4

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    DOI: 10.1021/bi0353651

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  • Transition state analysis of the coupling of drug transport to ATP hydrolysis by P-glycoprotein Reviewed

    MK Al-Shawi, MK Polar, H Omote, RA Figler

    JOURNAL OF BIOLOGICAL CHEMISTRY   278 ( 52 )   52629 - 52640   2003.12

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    DOI: 10.1074/jbc.M308175200

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  • A novel electron paramagnetic resonance approach to determine the mechanism of drug transport by P-glycoprotein Reviewed

    H Omote, MK Al-Shawi

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 47 )   45688 - 45694   2002.11

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    DOI: 10.1074/jbc.M206479200

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  • Synthase (H+ ATPase): coupling between catalysis, mechanical work, and proton translocation

    M Futai, H Omote, Y Sambongi, Y Wada

    BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS   1458 ( 2-3 )   276 - 288   2000.5

  • Use of chemical chaperones in the yeast Saccharomyces cerevisiae to enhance heterologous membrane protein expression: High-yield expression and purification of human P-glycoprotein Reviewed

    RA Figler, H Omote, RK Nakamoto, MK Al-Shawi

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   376 ( 1 )   34 - 46   2000.4

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  • Escherichia coli ATP synthase alpha subunit Arg-376: The catalytic site arginine does not participate in the hydrolysis/synthesis reaction but is required for promotion to the steady state

    NP Le, H Omote, Y Wada, MK Al-Shawi, RK Nakamoto, M Futai

    BIOCHEMISTRY   39 ( 10 )   2778 - 2783   2000.3

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    DOI: 10.1021/bi992530h

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  • Regulation and reversibility of vacuolar H+-ATPase

    T Hirata, N Nakamura, H Omote, Y Wade, M Futai

    JOURNAL OF BIOLOGICAL CHEMISTRY   275 ( 1 )   386 - 389   2000.1

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    DOI: 10.1074/jbc.275.1.386

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  • Mechanical rotation of the c subunit oligomer in ATP synthase (F0F1): direct observation. Reviewed

    Sambongi Y, Iko Y, Tanabe M, Omote H, Iwamoto-Kihara A, Ueda I, Yanagida T, Wada Y, Futai M

    Science (New York, N.Y.)   286 ( 5445 )   1722 - 1724   1999.11

  • The gamma-subunit rotation and torque generation in F-1-ATPase from wild-type or uncoupled mutant Escherichia coli

    H Omote, N Sambonmatsu, K Saito, Y Sambongi, A Iwamoto-Kihara, T Yanagida, Y Wada, M Futai

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   96 ( 14 )   7780 - 7784   1999.7

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    DOI: 10.1073/pnas.96.14.7780

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  • Stability of the Escherichia coli ATP synthase F0F1 complex is dependent on interactions between gamma Gln-269 and the beta subunit loop beta Asp-301-beta Asp-305 Reviewed

    H Omote, K Tainaka, K Fujie, A Iwamoto-Kihara, Y Wada, M Futai

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   358 ( 2 )   277 - 282   1998.10

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  • Essential Cys-Pro-Cys Motif of Caenorhabditis elegans Copper Transport ATPase Reviewed

    YOSHIMIZU Takao, OMOTE Hiroshi, WAKABAYASHI Tokumitsu, SAMBONGI Yoshihiro, FUTAI Masamitsu

    Bioscience, biotechnology, and biochemistry   62 ( 6 )   1258 - 1260   1998.6

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    Caenorhabditis elegans putative copper ATPase (CUA-1) had been functionally expressed in a yeast &lrtri;ccc2 mutant (copper ATPase gene disruptant). We found that CUA-1 with Cys-Pro-Cys to Cys-Pro-Ala mutation could not rescue the yeast &lrtri;ccc2 mutant, suggesting that the carboxyl terminal cysteine residue in the conserved Cys-Pro-Cys motif is essential for copper transport.

    DOI: 10.1271/bbb.62.1258

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    Other Link: https://jlc.jst.go.jp/DN/JALC/00085042551?from=CiNii

  • Mutational analysis of F1F0 ATPase: Catalysis and energy coupling Reviewed

    Omote, H., Futai, M.

    Acta Physiologica Scandinavica, Supplement   163 ( 643 )   1998

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  • Atomic force microscopy of Escherichia coli FoF1-ATPase in reconstituted membranes Reviewed

    Takeyasu, K., Omote, H., Nettikadan, S., Tokumasu, F., Iwamoto-Kihara, A., Futai, M.

    Annals of the New York Academy of Sciences   834 ( 1 Na/K-ATPase a )   149 - 152   1997.11

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    DOI: 10.1111/j.1749-6632.1997.tb52244.x

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  • Caenorhabditis elegans cDNA fro a Menkes/Wilson Disease Gene Homologue and Its Function in a Yeast CCC2 Gene Deletion Mutant^1

    SAMBONGI Yoshihiro, WAKABAYASHI Tokumitsu, YOSHIMIZU Takao, OMOTE Hiroshi, OKA Toshihiko, FUTAI Masamitsu

    Journal of Biochemistry   121 ( 6 )   1169 - 1175   1997.6

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  • Conformational transmission in ATP synthase during catalysis: Search for large structural changes Reviewed

    Futai, M., Omote, H.

    Journal of Bioenergetics and Biomembranes   28 ( 5 )   1996

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    DOI: 10.1007/BF02113982

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  • Molecular imaging of Escherichia coli F0F1-ATPase in reconstituted membranes using atomic force microscopy Reviewed

    Takeyasu, K., Omote, H., Nettikadan, S., Tokumasu, F., Iwamoto-Kihara, A., Futai, M.

    FEBS Letters   392 ( 2 )   1996

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    DOI: 10.1016/0014-5793(96)00796-X

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  • Chapter 3 F-type H+ ATPase (ATP synthase): Catalytic site and energy coupling Reviewed

    Futal, M., Omote, H.

    Handbook of Biological Physics   2 ( C )   1996

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    DOI: 10.1016/S1383-8121(96)80044-3

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  • Escherichia coli H+-ATPase (ATP synthase): Catalytic site and roles of subunit interactions in energy coupling Reviewed

    M Futai, H Omote, M Maeda

    BIOCHEMICAL SOCIETY TRANSACTIONS   23 ( 4 )   785 - 789   1995.11

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  • BETA-SUBUNIT GLU-185 OF ESCHERICHIA-COLI H+-ATPASE (ATP SYNTHASE) IS AN ESSENTIAL RESIDUE FOR COOPERATIVE CATALYSIS Reviewed

    H OMOTE, NP LE, MY PARK, M MAEDA, M FUTAI

    Journal of Biological Chemistry   270 ( 43 )   25656 - 25660   1995.10

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    DOI: 10.1074/jbc.270.43.25656

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  • BETA-GAMMA SUBUNIT INTERACTION IS REQUIRED FOR CATALYSIS BY H+-ATPASE (ATP SYNTHASE) - BETA-SUBUNIT AMINO-ACID REPLACEMENTS SUPPRESS A GAMMA-SUBUNIT MUTATION HAVING A LONG UNRELATED CARBOXYL-TERMINUS Reviewed

    C JEANTEURDEBEUKELAER, H OMOTE, A IWAMOTOKIHARA, M MAEDA, M FUTAI

    JOURNAL OF BIOLOGICAL CHEMISTRY   270 ( 39 )   22850 - 22854   1995.9

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  • CONSERVED GLU-181 AND ARG-182 RESIDUES OF ESCHERICHIA-COLI H+-ATPASE (ATP SYNTHASE) BETA-SUBUNIT ARE ESSENTIAL FOR CATALYSIS - PROPERTIES OF 33 MUTANTS BETWEEN BETA-GLU-181 AND BETA-LYS-801 RESIDUES Reviewed

    MY PARK, H OMOTE, M MAEDA, M FUTAI

    JOURNAL OF BIOCHEMISTRY   116 ( 5 )   1139 - 1145   1994.11

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  • ATP SYNTHASE (F0F1-ATPASE) - MUTATIONAL ANALYSIS OF CATALYTIC AND COUPLING MECHANISM

    A IWAMOTO, H OMOTE, MY PARK, M MAEDA, M FUTAI

    PROTEIN ENGINEERING   7 ( 9 )   1171 - 1171   1994.9

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  • CATALYSIS AND ENERGY COUPLING OF H+-ATPASE (ATP SYNTHASE) - MOLECULAR BIOLOGICAL APPROACHES Reviewed

    M FUTAI, MY PARK, A IWAMOTO, H OMOTE, M MAEDA

    BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS   1187 ( 2 )   165 - 170   1994.8

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  • THE ALPHA/BETA SUBUNIT INTERACTION IN H+-ATPASE (ATP SYNTHASE) - AN ESCHERICHIA-COLI ALPHA-SUBUNIT MUTATION (ARG-ALPHA-296 -] CYS) RESTORES COUPLING EFFICIENCY TO THE DELETERIOUS BETA-SUBUNIT MUTANT (SER-BETA-174 -] PHE) Reviewed

    H OMOTE, MY PARK, M MAEDA, M FUTAI

    JOURNAL OF BIOLOGICAL CHEMISTRY   269 ( 14 )   10265 - 10269   1994.4

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  • Osmoenzyme-H(+)-ATP synthase: catalysis and H+ translocation

    Futai, M., Omote, H., Maeda, M.

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   39 ( 7 )   1994

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  • ESCHERICHIA-COLI F0F1-ATPASE - RESIDUES INVOLVED IN CATALYSIS AND COUPLING Reviewed

    RK NAKAMOTO, K SHIN, A IWAMOTO, H OMOTE, M MAEDA, M FUTAI

    ANNALS OF THE NEW YORK ACADEMY OF SCIENCES   671   335 - 344   1992.11

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  • ESCHERICHIA-COLI ATP SYNTHASE (F-ATPASE) - CATALYTIC SITE AND REGULATION OF H+ TRANSLOCATION Reviewed

    M FUTAI, A IWAMOTO, H OMOTE, Y ORITA, K SHIN, RK NAKAMOTO, M MAEDA

    JOURNAL OF EXPERIMENTAL BIOLOGY   172   443 - 449   1992.11

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  • EFFECTS OF MUTATIONS OF CONSERVED LYS-155 AND THR-156 RESIDUES IN THE PHOSPHATE-BINDING GLYCINE-RICH SEQUENCE OF THE F1-ATPASE-BETA SUBUNIT OF ESCHERICHIA-COLI Reviewed

    H OMOTE, M MAEDA, M FUTAI

    JOURNAL OF BIOLOGICAL CHEMISTRY   267 ( 29 )   20571 - 20576   1992.10

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  • A GLYCINE-RICH SEQUENCE IN THE CATALYTIC SITE OF F-TYPE ATPASE

    M FUTAI, A IWAMOTO, H OMOTE, M MAEDA

    JOURNAL OF BIOENERGETICS AND BIOMEMBRANES   24 ( 5 )   463 - 467   1992.10

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  • ESCHERICHIA-COLI F0F1-ATPASE - RESIDUES INVOLVED IN CATALYSIS AND COUPLING Reviewed

    RK NAKAMOTO, K SHIN, A IWAMOTO, H OMOTE, M MAEDA, M FUTAI

    ION-MOTIVE ATPASES : STRUCTURE, FUNCTION, AND REGULATION   671   335 - 344   1992

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  • MUTATIONS IN SER174 AND THE GLYCINE-RICH SEQUENCE (GLY149, GLY150, AND THR156) IN THE BETA-SUBUNIT OF ESCHERICHIA-COLI H+-ATPASE Reviewed

    A IWAMOTO, H OMOTE, H HANADA, N TOMIOKA, A ITAI, M MAEDA, M FUTAI

    JOURNAL OF BIOLOGICAL CHEMISTRY   266 ( 25 )   16350 - 16355   1991.9

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MISC

  • 神経因性・炎症性疼痛に有効な小胞型ヌクレオチドトランスポーターの特異的阻害剤の同定

    加藤 百合, 日浅 未来, 市川 玲子, 蓮澤 奈央, 門脇 敦志, 岩槻 健, 島 和弘, 遠藤 康男, 北原 吉朗, 井上 剛, 野村 政壽, 表 弘志, 森山 芳則, 宮地 孝明

    脂質生化学研究   60   54 - 56   2018.5

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  • 恒常性維持のためのホルモン分泌調節 小胞型ヌクレオチドトランスポーター(VNUT)による内分泌制御

    表 弘志, 坂本 昌平, 宮地 孝明, 日浅 未来, 市川 玲子, 岩槻 健, 畝山 寿之, 高柳 涼一, 野村 政壽, 森山 芳則

    日本内分泌学会雑誌   90 ( 1 )   207 - 207   2014.4

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  • Vesicular neurotransmitter transporters : their structure and function

    245 ( 1 )   69 - 73   2013.4

  • 神経伝達物質トランスポーターの新展開 小胞型神経伝達物質トランスポーター 小胞型グルタミン酸トランスポーターの機能と制御

    表弘志, 宮地孝明

    脳21   14 ( 4 )   2011

  • [Localization mechanism of vesicular neurotransmitter transporters]. Reviewed

    Omote, H., Moriyama, Y.

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   53 ( 16 Suppl )   2220 - 2224   2008.12

Presentations

  • 巨核芽球細胞および血小板におけるポリアミン放出と小胞型ポリアミントランスポーターの発現

    表 弘志, 上原 美瑞紀, 福本 彩夏, 日浅 未来

    トランスポーター研究会  2025.5.31 

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    Event date: 2025.5.31 - 2025.6.1

    Language:Japanese   Presentation type:Poster presentation  

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  • Polyamine release and vesicular polyamine transporter expression in megakaryoblastic cells and platelets

    Hiroshi Omote, Mizuki Uehara, Ayaka Fukumoto, Miki Hiasa

    nternational Conference on the Biological Roles of Polyamines 2024, 7th Yamada Symposium  2024.8.26 

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    Event date: 2024.8.25 - 2024.8.29

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  • Vesicular polyamine transporter mediates vesicular storage and release of polyamine from MEG-01 cells

    Mizuki Uehara, Ayaka Fukumoto, Yuika Harada, Miki Hiasa, Hiroshi Omote

    2021.12.18 

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    Event date: 2021.12.18

    Presentation type:Oral presentation (general)  

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  • Vesicular polyamine transporter mediates vesicular storage and release of polyamine from MEG-01 cells

    Mizuki Uehara, Ayaka Fukumoto, Yuika Harada, Miki Hiasa, Hiroshi Omote

    Japan Bioenergetics Group  2021.12.17 

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    Event date: 2021.12.16 - 2021.12.17

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • Ⅱ型肺胞上皮細胞における小胞型ポリアミントランスポーターの発現と機能解析

    日浅 未来, 早形 奏美, 園山 和花子, 上原 美瑞紀, 福本 彩加, 表 弘志

    トランスポーター研究会  2025.5.31 

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    Event date: 2025.5.31 - 2025.6.1

    Language:Japanese  

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  • GLUT8は副腎クロマフィン細胞でのノルアドレナリン合成に関わっている

    公文 里穂, 吉馴 美穂, 土岐 達也, 山本 弘輝, 三谷 真智子, 森山 芳則, 日浅 未来, 表 弘志

    第19回トランスポーター研究会年会  2025.5.31 

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    Event date: 2025.5.1 - 2025.6.1

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  • Polyamine secretion to alveolar space through vesicular polyamine transporter (VPAT)

    Hiroshi omote, wakako sonoyama, mizuki uehara, miki hiasa

    Japan Bioenergetics Group  2024.12.12 

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    Event date: 2024.12.12 - 2024.12.14

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • Expression and function of vesicular polyamine transporter in lung alveolar epithelial cells

    Miki Hiasa, Wakako Sonoyama, Ayaka Fukumoto, Kanami Hayakata, Mizuki Uehara, Hiroshi Omote

    International Conference on the Biological Roles of Polyamines 2024 7th Yamada Symposium  2024.8.26 

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    Event date: 2024.8.25 - 2024.8.29

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  • 小胞型ポリアミントランスポーターは血小板および MEG-01 細胞からのポリ アミン分泌に関与する

    表弘志, 上原美瑞紀, 福本彩夏, 原田結加, 日浅未来

    日本生化学会 中国四国支部例会  2024.6.2 

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    Event date: 2024.6.1 - 2024.6.2

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • グルコーストランスポーター(GLUT8)は副腎クロマフィン細胞でのノルアドレナリン合成に関わっている

    表 弘志, 吉馴美穂, 土岐達也, 山本弘輝, 三谷真智子, 森山芳則, 日浅未来

    日本生体エネルギー研究会  2023.12.15 

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    Event date: 2023.12.14 - 2023.12.16

    Language:Japanese   Presentation type:Poster presentation  

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  • グルコーストランスポーター(GLUT8)は副腎クロマフィン細胞でのノルアドレナリン合成に関わっている

    吉馴美穂, 土岐達也, 山本弘輝, 三谷真智子, 森山芳則, 日浅未来, 表弘志

    日本生化学会中国四国支部会  2023.5.28 

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    Event date: 2023.5.27 - 2023.5.28

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • グルコーストランスポーターGLUT12の輸送機能と組織化学的解析

    表弘志, 松尾俊介, 土岐達也, 日浅未来

    日本生体エネルギー研究会  2020.12.11 

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    Event date: 2020.12.9 - 2020.12.11

    Presentation type:Oral presentation (general)  

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  • 小胞型ヌクレオチドトランスポーターにおけるCl-イオンと必須アルギニン残基の役割

    表弘志, 岩井佑磨, 釜谷節子, 森山佐和子, 森山芳則

    日本生体エネルギー研究会  2019.12.21 

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    Event date: 2019.12.20 - 2019.12.22

    Presentation type:Oral presentation (general)  

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  • 骨粗鬆症治療薬クロドロン酸は小胞型ヌクレオチドトランスポーターを標的として慢性疼痛を改善する

    加藤 百合, 日浅 未来, 市川 玲子, 蓮澤 奈央, 門脇 敦史, 岩槻 健, 島 和弘, 遠藤 康男, 北原 吉郎, 井上 剛, 野村 政壽, 表 弘志, 森山 芳則, 宮地 孝明

    生命科学系学会合同年次大会  2017.12  生命科学系学会合同年次大会運営事務局

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    Event date: 2017.12

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  • 小胞型ヌクレオチドトランスポーター特異的阻害剤を用いたプリン作動性化学伝達のin vivo制御

    加藤 百合, 日浅 未来, 門脇 敦志, 島 和弘, 市川 玲子, 岩槻 健, 北原 吉朗, 井上 剛, 遠藤 康男, 表 弘志, 森山 芳則, 宮地 孝明

    日本生化学会大会プログラム・講演要旨集  2016.9  (公社)日本生化学会

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    Event date: 2016.9

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  • 小胞型ヌクレオチドトランスポーター特異的阻害剤の同定とプリン作動性化学伝達のin vivo制御

    加藤 百合, 日浅 未来, 門脇 敦志, 島 和弘, 市川 玲子, 岩槻 健, 北原 吉朗, 井上 剛, 遠藤 康男, 表 弘志, 森山 芳則, 宮地 孝明

    日本薬学会年会要旨集  2016.3  (公社)日本薬学会

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    Event date: 2016.3

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  • 葉緑体ビタミンCトランスポーターの同定とその生理的役割

    宮地孝明, 黒森崇, 竹内優, 山地直樹, 横正健剛, 嶋澤厚, 杉本絵理子, 表弘志, 馬建鋒, 篠崎一雄, 森山芳則, 森山芳則

    トランスポーター研究会年会抄録集  2015.6.20 

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    Event date: 2015.6.20

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  • 葉特異的な発現をするタバコMATE型トランスポーターNt-JAT2の機能解析

    士反伸和, 南翔太, 森田匡彦, 林田南帆, 伊藤慎悟, 高梨功次郎, 杉山暁史, 表弘志, 森山芳則, GOOSSENS Alain, 守安正恭, 矢崎一史

    日本農芸化学会大会講演要旨集(Web)  2015 

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    Event date: 2015

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  • 葉緑体のアスコルビン酸トランスポーターの同定とその生理的役割

    宮地孝明, 黒森崇, 竹内優, 山地直樹, 横正健剛, 嶋澤厚, 杉本絵理子, 表弘志, 馬建鋒, 篠崎一雄, 森山芳則

    日本薬学会年会要旨集(CD-ROM)  2015 

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    Event date: 2015

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  • Vesicular nucleotide transporter (Vnut) regulates glucose metabolism.

    Shohei Sakamoto, Takaaki Miyaji, Miki Hiasa, Reiko Ichikawa, Akira Uematsu, Ken Iwatsuki, Atsushi Shibata, Hisayuki Uneyama, Ryoichi Takayanagi, Akitsugu Yamamoto, Hiroshi Omote, Masatoshi Nomura, Yoshinori Moriyama

    PURINERGIC SIGNALLING  2014.12 

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    Event date: 2014.12

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  • Inhibitors of ATP release inhibit vesicular nucleotide transporter

    Yuri Kato, Hiroshi Omote, Takaaki Miyaji

    PURINERGIC SIGNALLING  2014.12 

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    Event date: 2014.12

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  • Divalent cation transport by vesicular nucleotide transporter

    Takaaki Miyaji, Keisuke Sawada, Hiroshi Omote, Yoshinori Moriyama

    PURINERGIC SIGNALLING  2014.12 

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    Event date: 2014.12

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  • Characterization of transport properties of purified vesicular inhibitory amino acid transporter (VIAAT)

    Narinobu Juge, Akiko Muroyama, Miki Hiasa, Hiroshi Omote, Yoshinori Moriyama

    NEUROSCIENCE RESEARCH  2009 

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    Event date: 2009

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  • Identification and characterization of a vesicular nucleotide transporter

    Keisuke Sawada, Miki Hiasa, Noriko Echigo, Narinobu Juge, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama

    NEUROSCIENCE RESEARCH  2009 

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    Event date: 2009

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  • Biochemical characterization of purified vesicular inhibitory amino acid transporter (VIAAT)

    O. Narinobu Juge, Akiko Muroyama, Miki Hiasa, Hiroshi Omote, Yoshinori Moriyama

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN  2008 

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    Event date: 2008

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  • Identification and characterization of a vesicular nucleotide transporter

    Keisuke Sawada, Noriko Echigo, Narinobu Juge, Takaaki Miyaji, Miki Hiasa, Masato Otsuka, Hiroshi Omote, Yoshinori Moriyama

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN  2008 

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    Event date: 2008

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  • Functional characterization of mouse MATE2: a class 3 MATE-type polyspecific H+/organic cation exporter

    Miki Hiasa, Takuya Matsumoto, Toshinori Komatsu, Kojiro Ishikawa, Hiroshi Omote, Yoshinori Moriyama

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN  2007 

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    Event date: 2007

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  • A novel variant of mouse MATE-1 H+/organic cation exporter

    Ayumi Kobara, Miki Hiasa, Takuya Matsumoto, Masato Otsuka, Hiroshi Omote, Yoshinori Moriyama

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN  2007 

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    Event date: 2007

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  • L-glutamate signaling regulates transcytotic vesicle function in osteoclasts.

    S. Uehara, R. Morimoto, S. Yatsushiro, N. Juge, M. Hayashi, S. Senoh, T. Mizoguchi, T. Ninomiya, N. Udagawa, Z. Hua, H. Omote, A. Yamamoto, R. H. Edwards, Y. Moriyama

    JOURNAL OF BONE AND MINERAL RESEARCH  2006.9 

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    Event date: 2006.9

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  • Molecular dynamics and essential dynamics studies of the interaction of transported drugs with p-glycoprotein

    MK Al-Shawi, H Omote

    BIOPHYSICAL JOURNAL  2005.1 

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    Event date: 2005.1

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  • Interaction of transported drugs with the lipid bilayer and pglycoprotein: Drug transport is mediated by a hydration exchange mechanism

    H Omote, MK Al-Shawi

    BIOPHYSICAL JOURNAL  2004.1 

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    Event date: 2004.1

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  • 3SD03 Structure and mechanism of drug transport by P-glycoprotein

    Omote H., Al-Shawi Marwan K.

    Seibutsu Butsuri  2004  The Biophysical Society of Japan General Incorporated Association

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    Event date: 2004

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  • A novel EPR approach to determine the mechanism of drug transport by P-glycoprotein

    MK Al-Shawi, H Omote

    BIOPHYSICAL JOURNAL  2002.1 

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    Event date: 2002.1

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  • Coupling of drug transport to ATP hydrolysis by P-glycoprotein

    MK Al-Shawi, MK Polar, H Omote, RA Figler

    BIOPHYSICAL JOURNAL  2001.1 

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    Event date: 2001.1

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  • Mutations in the ATP synthase gene suppress the lethal effect by human Bax against bacteria

    NISHIMAKI Kiyomi, ASOH Sadamitu, OMOTE Hiroshi, HUTAI Masamitu, OHTA Shigeo

    1998.12.1 

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    Event date: 1998.12.1

    Language:Japanese  

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  • 線虫C. elegansの銅イオン輸送ATPaseのcDNAクローニングと酵母での発現

    三本木 至宏, 若林 篤光, 岡 敏彦, 表 弘志, 二井 將光

    日本分子生物学会年会プログラム・講演要旨集  1996.8.1 

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    Event date: 1996.8.1

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  • ATP合成酵素のβAsp301-βSer307領域とγサブユニットの相互作用

    對中 健一, 藤江 一成, 表 弘志, 二井 將光

    日本分子生物学会年会プログラム・講演要旨集  1996.8.1 

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    Event date: 1996.8.1

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  • 大腸菌F_0F_1-ATP合成酵素の反応機構

    表 弘志, LE Nga p., 藤江 一成, 對中 健一, 二井 將光

    日本分子生物学会年会プログラム・講演要旨集  1996.8 

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    Event date: 1996.8

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  • 副腎髄質における小胞型ポリアミントランスポーターの発現と生理作用の解明

    鈴木夏未, 表弘志, 日浅未来

    トランスポーター研究会  2025.5.31 

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  • II型肺胞上皮細胞における細胞外ポリアミンの生理作用

    日浅未来, 園山和花子, 上原美瑞紀, 福本彩加, 表弘志

    日本ポリアミン学会第 14 回年会  2023.12.23 

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  • グルコーストランスポーター(GLUT8)は 副腎クロマフィン細胞でのノルアドレナリン合成に関わっている

    表弘志, 吉馴 美穂, 土岐 達也, 山本 弘輝, 三谷 真智子, 森山 芳則, 日浅 未来

    日本生体エネルギー研究会 第48回討論会  2022.12 

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  • Biochemical and mutational analysis of Plasmodium falciparum chloroquine resistance transporter (PfCRT)

    Narinobu Juge, Tomomi Kinoshita, Haruka Iwai, Tomoya Fukui, Sawako Moriyama, Takaaki Miyaji, Yoshinori Moriyama, Hiroshi Omote

    2020.3.26 

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  • 小胞型ヌクレオチドトランスポーターのアロステリック制御

    表 弘志

    第55回 日本生物物理学会年会  2017.9.21 

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  • Identification and Drug Discovery of the Vesicular Nucleotide Transporter

    OMOTE Hiroshi

    2017.3 

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  • 蛍光型ATPアナログを用いた小胞型ヌクレオチドトランスポーターの機能解析

    表 弘志

    第38回 生体膜と薬物の相互作用シンポジウム  2016.11 

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  • トランスポータ-をターゲットとしたスクリーニング系の構築

    表 弘志

    岡山技術説明会  2016.1 

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  • マラリア原虫のクロロキン耐性トランスポーターの機能

    表 弘志

    日本生体エネルギー研究会 第41回討論会  2015.12 

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  • Functional Analysis of Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT) with Purified Protein

    表 弘志

    日本生化学会  2015.12 

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  • マラリア原虫クロロキン耐性トランスポーターの精製再構成系による機能解析

    表 弘志

    第37回生体膜と薬物の相互作用シンポジウム  2015.11 

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  • マラリア原虫のクロロキン耐性トランスポーター:PfCRTはH+共役型のアミノ酸やカチオン性薬物の輸送体である Invited

    表 弘志

    1. 第75回 日本寄生虫学会東日本支部会  2015.9.26 

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  • Functional analysis of Plasmodium falciparum chloroquine resistance transporter (PfCRT) by reconstituted system with purified protein

    表 弘志

    第53回日本生物物理学会  2015.9 

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  • 小胞型ヌクレオチドトランスポーター(VNUT)は血糖値の制御に関わる

    表 弘志

    日本薬学会 第135年会  2015.3 

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  • 小胞型ポリアミントランスポーターの同定

    表 弘志

    日本生体エネルギー研究会 第40回討論会  2014.12 

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  • 小胞型ポリアミントランスポーターの同定

    表 弘志

    第36回 生体膜と薬物の相互作用シンポジウム  2014.11 

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  • 精製再構成法を用いた新規トランスポーター機能の発見

    表 弘志

    第87回日本生化学会大会  2014.10 

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  • 小胞型ヌクレオチドトランスポーター(VNUT)による内分泌制御

    表 弘志

    第87回日本内分泌学会  2014.4 

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  • MATE型薬物輸送トランスポーターの薬物相互作用

    表 弘志

    第35回生体膜と薬物の相互作用シンポジウム  2013.11 

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  • 精製再構成系が明らかにする小胞型神経伝達物質トランスポーターと疾患の関わり

    表 弘志

    第86回日本生化学会大会  2013.9 

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  • 炎症性腸疾患抑制剤

    市川 玲子, 須賀 泰世, 北原 吉朗, 森山 芳則, 宮地 孝明, 表 弘志, 加藤 百合

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    Applicant:国立大学法人 岡山大学

    Application no:JP2017001824  Date applied:2017.1.19

    Announcement no:WO2017-126637  Date announced:2017.7.27

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  • アスコルビン酸トランスポーター

    森山 芳則, 宮地 孝明, 表 弘志, 黒森 崇, 篠崎 一雄

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    Applicant:国立大学法人 岡山大学

    Application no:特願2016-528627  Date applied:2014.7.15

    Announcement no:特表2016-526897  Date announced:2016.9.8

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  • ポリアミンの化学伝達を司るトランスポーターの同定とその利用

    森山 芳則, 表 弘志, 宮地 孝明, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:特願2014-544325  Date applied:2013.11.1

    Patent/Registration no:特許第6278467号  Date issued:2018.1.26

    J-GLOBAL

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  • ポリアミンの化学伝達を司るトランスポーターの同定とその利用

    森山 芳則, 表 弘志, 宮地 孝明, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:JP2013006488  Date applied:2013.11.1

    Announcement no:WO2014-068991  Date announced:2014.5.8

    J-GLOBAL

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  • アスコルビン酸トランスポーター

    森山 芳則, 宮地 孝明, 表 弘志, 黒森 崇, 篠崎 一雄

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    Applicant:国立大学法人 岡山大学

    Application no:特願2013-155640  Date applied:2013.7.26

    Announcement no:特開2015-023831  Date announced:2015.2.5

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  • 興奮性化学伝達調節剤およびそのスクリーニング法

    森山 芳則, 表 弘志, 樹下 成信

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    Applicant:国立大学法人 岡山大学

    Application no:JP2009055208  Date applied:2009.3.17

    Announcement no:WO2009-116546  Date announced:2009.9.24

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  • 興奮性化学伝達調節剤およびそのスクリーニング法

    森山 芳則, 表 弘志, 樹下 成信

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    Applicant:国立大学法人 岡山大学

    Application no:特願2010-503889  Date applied:2009.3.17

    Patent/Registration no:特許第5630750号  Date issued:2014.10.17

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  • アスパラギン酸の化学伝達を司るトランスポーターの同定とその利用

    森山 芳則, 表 弘志, 宮地 孝明, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:JP2008059079  Date applied:2008.5.16

    Announcement no:WO2008-143192  Date announced:2008.11.27

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  • アスパラギン酸の化学伝達を司るトランスポーターの同定とその利用

    森山 芳則, 表 弘志, 宮地 孝明, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:特願2008-552574  Date applied:2008.5.16

    Patent/Registration no:特許第5317056号  Date issued:2013.7.19

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  • 哺乳動物における新規SLC17型トランスポータータンパク質およびその利用

    森山 芳則, 表 弘志, 澤田 啓介

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    Applicant:国立大学法人 岡山大学

    Application no:JP2008053878  Date applied:2008.3.4

    Announcement no:WO2008-126517  Date announced:2008.10.23

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  • 哺乳動物における新規SLC17型トランスポータータンパク質およびその利用

    森山 芳則, 表 弘志, 澤田 啓介

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    Applicant:国立大学法人 岡山大学

    Application no:特願2008-526701  Date applied:2008.3.4

    Patent/Registration no:特許第5219146号  Date issued:2013.3.15

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  • 哺乳動物における新規トランスポータータンパク質およびその利用

    森山 芳則, 表 弘志, 大塚 正人, 松本 拓也, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:特願2007-203399  Date applied:2007.8.3

    Announcement no:特開2008-054675  Date announced:2008.3.13

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  • 哺乳動物における新規トランスポータータンパク質およびその利用

    森山 芳則, 表 弘志, 大塚 正人, 松本 拓也, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:特願2007-203399  Date applied:2007.8.3

    Announcement no:特開2008-054675  Date announced:2008.3.13

    Patent/Registration no:特許第5590590号  Date issued:2014.8.8

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  • 哺乳動物における新規トランスポータータンパク質およびその利用

    森山 芳則, 表 弘志, 大塚 正人, 松本 拓也, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:特願2007-203497  Date applied:2007.8.3

    Announcement no:特開2008-022855  Date announced:2008.2.7

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  • 哺乳動物における新規トランスポータータンパク質およびその利用

    森山 芳則, 表 弘志, 大塚 正人, 松本 拓也, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:JP2007057134  Date applied:2007.3.30

    Announcement no:WO2008-044351  Date announced:2008.4.17

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  • 哺乳動物における新規トランスポータータンパク質およびその利用

    森山 芳則, 表 弘志, 大塚 正人, 松本 拓也, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:特願2008-538574  Date applied:2007.3.30

    Patent/Registration no:特許第5167547号  Date issued:2013.1.11

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  • 哺乳動物における新規トランスポータータンパク質およびその利用

    森山 芳則, 表 弘志, 大塚 正人, 松本 拓也, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:特願2007-071536  Date applied:2007.3.19

    Announcement no:特開2008-011853  Date announced:2008.1.24

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  • 哺乳動物における新規トランスポータータンパク質およびその利用

    森山 芳則, 表 弘志, 大塚 正人, 松本 拓也, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:特願2006-275623  Date applied:2006.10.6

    Announcement no:特開2008-011848  Date announced:2008.1.24

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  • 哺乳動物における新規トランスポータータンパク質およびその利用

    森山 芳則, 表 弘志, 大塚 正人, 松本 拓也, 日浅 未来

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    Applicant:国立大学法人 岡山大学

    Application no:特願2006-275623  Date applied:2006.10.6

    Announcement no:特開2008-011848  Date announced:2008.1.24

    Patent/Registration no:特許第4752068号  Date issued:2011.6.3

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Awards

  • 文部科学大臣賞

    2014   文部科学省   「医学薬学的に重要なトランスポーターの発見と解析技術の研究」

    表 弘志

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Research Projects

  • ノルアドレナリン合成に関わる小胞型アスコルビン酸トランスポーターの同定

    Grant number:21K06068  2021.04 - 2024.03

    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)

    表 弘志

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

    ノルアドレナリンは自律神経から分泌される主要ホルモンの1つであり、副腎のクロマフィン細胞でドーパミンから生合成されている。この過程はクロマフィン細胞に存在するクロマフィン顆粒(分泌小胞)内で行われ、アスコルビン酸を必須因子としている。基質になるドーパミンは小胞型モノアミントランスポーター(VMAT)によって顆粒内に取り込まれ、その後DβH(ドーパミンβヒドロキシラーゼ)によって水酸化されてノルアドレナリンに変換される。この酵素はアスコルビン酸を補酵素とするため、ノルアドレナリン生合成にアスコルビン酸が不可欠となっている。実際、クロマフィン顆粒内にはノルアドレナリンとともにアスコルビン酸が蓄積していることが知られていた。
    このように、ノルアドレナリン生合成の概要は明らかになっているかのように見えるが、アスコルビン酸は必須因子であるにも関わらず、クロマフィン顆粒内に輸送・蓄積するトランスポーターは未だ見つかっていない。これまでにアスコルビン酸トランスポーターを同定する試みが行われてきたが、いずれも当該トランスポーターの発見には至らなかった。我々は発想を変え、酸化型のアスコルビン酸が小胞内に輸送された後、還元されるものと考えた。
    本研究ではこれまでの解析から、細胞内膜型グルコーストランスポーターがアスコルビン酸を小胞に運ぶトランスポーターの実体であると考え、GLUT8を候補トランポーターとして選定した。本年度はGLUT8の細胞内局在解析および、クロマフィン顆粒を用いたノルアドレナリン合成活性測定系の確立を行なった。単離クロマフィン細胞を用いた免疫組織化学的解析から、GLUT8はクロマフィン顆粒に存在するものと推定された。

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  • Identification of the vesicular ascorbic acid transport system

    Grant number:17K07336  2017.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Hiroshi Omote

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    Grant amount:\4810000 ( Direct expense: \3700000 、 Indirect expense:\1110000 )

    Dopamine-beta-hydroxylase catalyzes conversion of dopamine to noradrenaline in the lumen of chromaffin granule of adrenal cortex. This enzyme requires ascorbic acid (vitamin C) as a cofactor. Previous studies indicated that ascorbic acid is accumulated in this granule. However, molecular mechanism of ascorbic acid transport to this granule was not understood yet. In this study, we tried to identify the transporter responsible to vesicular ascorbic acid accumulation and reveal molecular mechanism of ascorbic acid transport to the vesicle.
    We successfully identified the vesicular transport the is located in the chromaffin granule of adrenal cortex by PCR, immunohistochemistry and western blot analyses.

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  • Novel Transport Assay System by SPA Method

    Grant number:25650035  2013.04 - 2015.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    OMOTE Hiorshi

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

    Membrane transporters play essential roles in various cellular activities such as nutrient uptake, control of drug concentration and neuronal signal transmission. Therefore, measurement of transport activity is important for basic biology, medical science and pharmacology. So far, function of transporters is measured using heterologous expression system. However, it has difficulty due to artifact by other transporters presented in the cells.
    In this study, we have aimed to develop novel transport assay system with SPA method. In this system, purified transporter is embedded in the liposomes and attached to SPA scintillation beads through appropriate tags. We found that this technique is useful for future transporter study.

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  • Development of oriented reconstitution methods for membrane proteins

    Grant number:23657091  2011 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    OMOTE Hiroshi

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    Grant amount:\2990000 ( Direct expense: \2300000 、 Indirect expense:\690000 )

    Transporters contribute to various biological activity including uptake of nutrients, exclusion of waste products and drugs. It also contribute to signal transmission through their transport activity across the membrane. Measurement of transport activity is an essential part of functional study of transporters and development of novel drugs. In this study, we investigated the transport assay with reconstituted liposomes.

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  • Molecular mechanism of the multi-transportmachinery

    Grant number:21370057  2009 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    OMOTE Hiroshi

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    Grant amount:\18590000 ( Direct expense: \14300000 、 Indirect expense:\4290000 )

    The vesicular glutamate transporter (VGLUT) is a member of the SLC17 family and transports glutamate into synaptic vesicles using a membrane potential as a driving force. VGLUT plays essential roles in glutamatergic signal transmission. The SLC17 family members are unique transporter which two distinct transport activity ,membrane potential driven anion transport and Na^+ gradient driven inorganic phosphate transport. In this study, we investigated functional mechanism and roles of SLC17 transporters.

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  • 小胞型ヌクレオチドトランスポーターのATP認識機構

    Grant number:21118514  2009 - 2010

    日本学術振興会  科学研究費助成事業 新学術領域研究(研究領域提案型)  新学術領域研究(研究領域提案型)

    表 弘志

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    Grant amount:\5200000 ( Direct expense: \4000000 、 Indirect expense:\1200000 )

    ATPは生体エネルギー分子として様々な生命現象に深く関わっている。LohmannによるATPの発見以来、ATPの物理学的諸性質とエネルギー利用の分子メカニズムの解明の重要性が認識されてきた。ATP加水分解エネルギーの利用者である蛋白質側から見ると、ATP結合の様式はその後のエネルギー利用の方法を決定する重要なファクターである。したがって、ATP結合様式を理解する事はATPからエネルギーを取り出す仕組みを理解する上で必須なステップである。本研究は、新規のATP結合タンパク質である小胞型ヌクレオチドトランスポーター(VNUT)の解析を通して、蛋白質とATPの相互作用の全体像を理解し、生体内エネルギー分子としてのATPの理解に貢献するものである。
    VNUTは分泌小胞にATP等のヌクレオチドを輸送するトランスポーターであり、既存のATP結合タンパク質とは全く相同性がない。精製VNUTをリポソーム中に再構成し、人工膜電位を形成したところ、能動的なATPの輸送が見られた。この輸送は内側が正の膜電位によって駆動され、その活性に塩素イオンを必要とした。興味深い事に、ATPの輸送は2価金属イオンによって影響されなかった。2価金属イオン存在下ではATPは複合体を形成する。したがって、この結果はVNUTはATPとともに2価金属イオンも輸送している事を示唆している。実際Ca45を用いた輸送実験で、VNUTはATPとともにCaを輸送した。

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  • Transport Mechanism of Vesicular Glutamate Transporter

    Grant number:19570132  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    OMOTE Hiroshi

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

    小胞型グルタミン酸トランスポーター(VGLUT)はV-ATPaseがATPの加水分解によって形成するH+の電気化学的勾配を駆動力とし、グルタミン酸を小胞内に輸送するトランスポーターである。この研究ではVGLUTによるグルタミン酸輸送の分子機構を明らかにすべく、VGLUTを含むSLC17型ファミリートランスポーターの輸送機構を速度論的に解析した。

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  • 薬物排出の最終段階を担う新規有機カチオン輸送体の構造と機能及び相互作用

    Grant number:18059023  2006 - 2007

    日本学術振興会  科学研究費助成事業 特定領域研究  特定領域研究

    大塚 正人, 表 弘志

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    Grant amount:\4300000 ( Direct expense: \4300000 )

    申請者は現在までにMATEのプロトタイプのVibrio Parahaemolyticus由来のNorMに関して機能性アミノ酸残基を同定している(J Bacteriol,2005)。NorMの薬物輸送に関与する機能性アミノ酸残基は、膜貫通領域に存在している酸性アミノ酸残基であった。バクテリア由来のMATEトランスポーターのNorMは、ヒトMATE1とタンパク質レベルで23.6%の相同性しかないが、これらの酸性アミノ酸残基のうちの2つはヒト及びマウスのMATE1及びMATE2で保存されていた。以上のことから、哺乳類のMATEにおいてもこれらの酸性アミノ酸残基を含む極性アミノ酸残基が、MATEの基質認識機構や、プロトンとの交換輸送機構に直接関係していることが予想される。これらの予想を基にMATE1の点変異体を複数作製した。(MATEの極性残基部分:E278A,E319A,H386A,E389A 等)。そして、TEA(テトラエチルアンモニウム)の取り込み活性に与える影響をRIトレーサー実験により調べた。この結果より機能性アミノ酸残基を決定した。また、MATE1変異体の基質特異性や、輸送活性に及ぼすpHの影響に対する変化についても詳細に解析を行うことによって、OC/H+交換輸送における基質認識機構や、プロトンとの交換輸送機構を解明した。ヒトMATE1の膜貫通領域にある極性アミノ酸のうち、E273Qの点変異体を作成しHEK293細胞に発現させたところ、TEAの輸送活性は完全に消失した(PNAS 2005,)。また、MATE1の機能と構造を理解する上でその分子単体に注目し、大量発現・精製及びそのリポソームへの再構成系を確立した。大量発現系は、昆虫細胞を用いた発現系を用いた。また、大量発現したタンパク質を精製・リポソームに再構成し、活性の測定を行う系を構築した。こうした技術をMATEタンパク質の機能解析に応用した。そして輸送測定で基質とH^+の化学平衡か測定した。

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  • Molecular mechanism of substrate recognition and transport by P-glycoprotein

    Grant number:17570113  2005 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    OMOTE Hiroshi

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    Grant amount:\3500000 ( Direct expense: \3500000 )

    Broad substrate specificity of human P-glycoprotein (ABCB1) is an essential feature of multidrug resistance. Transport substrates of P-glycoprotein are mostly hydrophobic and many of them have net positive charge. These compounds partition into the membrane. Utilizing the energy of ATP hydrolysis, P-glycoprotein is thought to take up substrates from the cytoplasmic leaflet of the plasma membrane and to transport themto the outside of the cell. We examined this model by molecular dynamics simulation of the lipid bilayer, in the presence of transport substrates together with an atomic resolution structural model of P-glycoprotein. Taken together with previous electron paramagnetic resonance studies, the results suggest that most transported drugs are concentrated near the surface zone of the inner leaflet of the plasma membrane. Here the drugs can easily diffuse laterally into the drug-binding site of P-glycoprotein through an open cleft. It was concluded that the initial high-affinity drugbinding site was located in the interfacial surface area of P-glycoprotein in contact with the membrane interface. Based on these results and our recent kinetic studies, a "solvation exchange" drug transport mechanism of P-glycoprotein is discussed. A molecular basis for the improved colchicine transport efficiency by the much-studied colchicine-resistance G185V mutant human P-glycoprotein is also provided.

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  • シナプス小胞の形成と開口放出におけるリン脂質動態を制御する膜因子の構造と機能

    Grant number:17024042  2005

    日本学術振興会  科学研究費助成事業 特定領域研究  特定領域研究

    森山 芳則, 表 弘志

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    Grant amount:\2500000 ( Direct expense: \2500000 )

    シナプス小胞が開口放出される際、フォスファチジルセリン(PS)が脂質二重層の上層部に集積し融合を促進すると考えられている。このPSの膜内での輸送を司っていると考えられているのがPS依存性ATPaseである。本研究はこのPS依存性ATPaseの生化学的・細胞生物学的性質を明らかにすることを目的としている。成果は以下にまとめた。
    (1)PS依存性ATPaseをコードするcDNAをラット脳よりクローン化し、昆虫細胞を用いた発現系を構築した。
    (2)上記の発現系を用いて野生型ならびに変異型ATPaseを精製した。現在、その生化学的性質を解析中である。
    (3)PS依存性ATPaseに対する特異的モノクローン抗体2E6を作製した。Synaptophysinとの2重ラベル免疫電子顕微鏡法によりPS依存性ATPaseが確かにシナプス小胞に存在していることを証明した。
    (4)この抗体をPC12細胞に注入したところ分泌顆粒の開口放出が部分的に阻害された。
    以上の結果はPS依存性ATPaseは開口放出において本質的に重要であることを強く示唆している。

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  • 高等植物における液胞形成の制御と組織構築

    Grant number:10182208  1998

    日本学術振興会  科学研究費助成事業 特定領域研究(A)  特定領域研究(A)

    和田 洋, 岡 敏彦, 表 弘志

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    Grant amount:\3000000 ( Direct expense: \3000000 )

    液胞はその内部を酸性に保ち,液胞膜を介した化学浸透圧的エネルギー差を利用して代謝産.物・無機イオンを輸送する.高等植物の液胞膜を介した化学浸透圧エネルギー差は,H^+-ATPase,H^+-PPaseの二種のイオンポンプの機能による,本研究では、高等植物の形態・組織構築に果たす液胞の生理的機能を明らかに.する研究の一環としてオルガネラ酸性化の制御機構に焦点を結び,細胞基質と液胞のイオン環境の調節を分子レベルで解析する系の構築を進めた.シロイヌナズナの液胞膜H^+-PPaseのcDNA(AVP3)をライブラリーから取得し,これを出芽酵母の構成的かつ強発現性プロモータの下流において出芽酵母に導入した.細胞分画法・蛍光抗体法の両手法で,66-kDaのシロイヌナズナH^+-PPaseが出芽酵母の液胞に発現されることを確認した.この形質転換酵母より液胞膜小胞を単離し,ATP(出芽酵母内在性のH^+-ATPaseを駆動する),およびPPi(シロイヌナズナH^+-PPKSeを駆動する)依存に形成されるpH差.膜電位差を色素の蛍光クエンチングを指標に測定した.ATPase、PPaseの両者をもつ液胞膜小胞は,ATPもしくはPPi単独でH^+輸送を駆動したときよりも,ATP+PPiで駆動した場合の方が,大きなpH差を形成するが,一方,膜電位差は大きくは変わらない.このことは,液胞膜のイオン環境の制御には,膜電位差が重要な,おそらく制限的な因子として作用していることを示している.

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  • マラリア原虫における細胞内小胞輸送の分子機構

    Grant number:10166204  1998

    日本学術振興会  科学研究費助成事業 特定領域研究(A)  特定領域研究(A)

    和田 洋, 岡 敏彦, 表 弘志

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    Grant amount:\1700000 ( Direct expense: \1700000 )

    マラリア原虫の血球内生育サイクルにおいて,エンドサイトーシス・エクソサイトーシスといった細胞膜と細胞内小器官膜との間の小胞輸送過程が,原虫のエネルギー獲得と物質の取り込みに必須な役割を果たす.したがって,小胞輸送過程の分子機構の解明は,マラリア原虫の生育生理を理解する上で極めて重要であるのみならず,マラリア制圧に向けた新奇の戦略を構想する点においても重要である.しかしながら,本生物の細胞内小胞輸送の分子機構はほとんど明らかにされていない.細胞内小胞輸送に直接的に関与する分子として,N-ethylmaleimide sensitive fusion protcin(NSF)がPlasmodium falciparumのゲノム上に存在することを,Genomedatabaseの検索の結果,明らかにした.この分子の機能を,まず,出芽酵母発現系を用いて解析することを考え,酵母発現ベクターに遺伝子断片を組み込むことを進めている.しかしながら,Plasmodiumの遺伝子のAT-richである特性のため,通常の遺伝子操作法では特異的遺伝子断片の取得と同定が困難であり,現在のところ酵母での発現にまで至っていない.

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  • 大腸菌F_OF_1-ATP合成酵素の結晶化と立体構造の解析

    Grant number:09780546  1997 - 1998

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

    表 弘志

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    Grant amount:\2000000 ( Direct expense: \2000000 )

    本研究では、FoF_1-ATP合成酵素の立体構造を明らかにするため、FoF_1および、F_1の精製、及び予備的な結晶化条件の検索を行った。
    FoF_1-ATP合成酵素は、我々が既に報告している大量発現系を用いて、密度勾配遠心法により精製した。また、F_1は同じ発現系を用いて、カラムクロマトグラフィーにより精製した。このようにして調製したFoF_1を脂質二重膜に再構成し、AFMによる観察、二次元結晶化の条件の検索に用いた。また、F_1を用いて、蒸気拡散法による三次元結晶化を試みた。
    Foは膜内在性で、H^+の輸送部位を形成している。したがって、H^+輸送の機構を理解するためにはFoの構造を明らかにすることが必要である。これまでにa,b,cの3種のサブユニットから構成されていることが報告されている。しかし、これらのサブユニットの配置がどうなっているかはまだ明らかでなかった。本研究ではAFMを用いて、Foの表面構造を観察することにより、Foの各サブユニットの配置を推定した。また、F_1の3次元結晶化条件の予備的な検討を行い、基礎的なデー夕を得た。さらにFoのcサブユニットにCysを導入し、低温電子顕微鏡で観察する系を構築した。

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  • FoF_1-ATP合成酵素の高次構造の解析

    Grant number:08780560  1996

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

    表 弘志

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    Grant amount:\1100000 ( Direct expense: \1100000 )

    本研究では、FoF_1-ATP合成酵素の立体構造を明らかにするため、FoF_1および、Foの精製、2次元結晶化条件の検索を行った。また、脂質二重膜に再構成した精製酵素をAFM(原子間力顕微鏡)で表面観察した。これによって、膜内在性であるFoのサブユニットの配置に関する情報を得ることができた。
    FoF_1-ATP合成酵素は、我々が既に報告している大量発現系を用いて、密度勾配遠心により精製した。また、Foは精製FoF_1を尿素で処理した。この処理でF_1部分のサブユニットを解離させ、その後Fo部分を遠心操作により沈殿させた。これにより、精製度90%以上のFoを得ることができた。
    このようにして調製したFo及びFoF_1を脂質二重膜に再構成し、AFMによる観察、二次元結晶化の条件の検索に用いた。
    Foは膜内在性で、H^+の輸送部位を形成している。したがって、H^+輸送の機構を理解するためにはFoの構造を明らかにすることが必要である。これまでにa,b,cの3種のサブユニットから構成されていること、これらのサブユニットが1:2:10-12の量比で存在していることが報告されている。しかし、これらのサブユニットの配置がどうなっているかはまだ明らかでなかった。本研究ではAFMを用いて、Foの表面構造を観察することにより、Foの各サブユニットの配置を推定した。その結果、cサブユニットによる、リング状の構造物とa,bサブユニットからなると思われる膨らみを見いだした。これは、cサブユニットが形成するリングの外側にaとbサブユニットが配置していることを示している。

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  • Mechanism of H^+ transport by H^+ATPase

    Grant number:07458159  1995 - 1996

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    FUTAI Masamitsu, OKA Toshihiko

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    Grant amount:\7300000 ( Direct expense: \7300000 )

    H^+-ATPase transport protons coupling with the energy of ATP hydrosis, and ATP synthase synthesizes ATP coupling with proton movement. They are the two of the most the important basic enzymes in organisms. In this project, we have focused on FoF_1 type ATPase and vacuolar type ATPases.
    From the extensive mutagenesis studies, we could show Lys-155, Thr-156, Glu-181 and Arg-182 of the beta subunit are forming catalytic site. We also could show that Glu-185 of the subunit is essential for the catalytic cooperativity of the enzyme. The carboxyl and amino terminal helices of the gamma subunit were shown to be essential for energy coupling between catalysis and proton transport.
    The H^+ pathway of Fo is formed from the a, b, and c subunits we could show that the a subunit has six transmembrane domains and the entire Fo has a ring like structure. We have studied effects of a series of lipophilic cations on FoF_1-ATPase and vacuolar type ATPase and chloropromazine, quinacrine could in habit both enzymes. We also showed inhibitory effects of concanamycin on vacuolar type ATPase.

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