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A novel GDP-bound-Rab27a-interacting protein which regulates endocytosis of insulin secretory membranes

Research Project

Project/Area Number 23791039
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Metabolomics
Research InstitutionOita University

Principal Investigator

KIMURA Toshihide  大分大学, 医学部, 准教授 (60404373)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsIQGAP1 / Rab27a / エンドサイトーシス / 膵B細胞 / インスリン / 糖尿病 / Gタンパク質 / メンブレントラフィック / 低分子量Gタンパク質 / coronin
Research Abstract

Intracellular trafficking is a fundamental cellular process that is required for communication between organelles. Recruitment of specific molecules to specific membrane sites is essential for this trafficking. Rab27a, a member of the Rab GTPase family, has been considered to act as a molecular switch for exocytosis in insulin secretion, cycling between an active GTP-bound and an inactive GDP-bound state. I previously showed that GDP-bound Rab27a is not an inactive form but is in fact an active form that regulates endocytosis through the GDP-dependent effector coronin3. In the present study, I identified IQGAP1, an effector of GTP-bound Cdc42, as another GDP-dependent effector of Rab27a. My results indicate that activation of Cdc42 in response to the insulin secretagogue glucose recruits endocytic machinery, including GDP-bound Rab27a and coronin3, to IQGAP1 at the cell periphery and regulates endocytosis at this membrane site.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (51 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (27 results) (of which Invited: 2 results) Book (7 results) Remarks (4 results)

  • [Journal Article] Activated Cdc42-bound-IQGAP1 determines the cellular endocytic site2013

    • Author(s)
      Kimura T, Yamaoka M, Taniguchi S, Okamoto M, Takei M, Ando T, Iwamatsu A, Watanabe T, Kaibuchi K, Ishizaki T, Niki I
    • Journal Title

      Mol. Cell. Biol

      Volume: 33 Issue: 24 Pages: 4834-43

    • DOI

      10.1128/mcb.00895-13

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endogenous hydrogen sulfide protects pancreatic beta-cells from a high-fat diet-induced glucotoxicity and prevents the development of type 2 diabetes Biochem2013

    • Author(s)
      Okamoto M, Yamaoka M, Takei M, Ando T, Taniguchi S, Ishii I, Tohya K, Ishizaki T, Niki I, Kimura T
    • Journal Title

      Biophys. Res. Commun

      Volume: 442 Issue: 3-4 Pages: 227-233

    • DOI

      10.1016/j.bbrc.2013.11.023

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activated Cdc42-bound-IQGAP1 determines the cellular endocytic site2013

    • Author(s)
      Kimura T, Yamaoka M, Taniguchi T, Okamoto M, Takei M, Ando T, Iwamatsu A, Watanabe T, Kaibuchi K, Ishizaki T, Niki I
    • Journal Title

      Mol. Cell. Biol.

      Volume: 33 Pages: 4834-4843

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endogenous hydrogen sulfide protects pancreatic beta-cells from a high-fat diet-induced glucotoxicity and prevents the development of type 2 diabetes2013

    • Author(s)
      Okamoto M, Yamaoka M, Takei M, Ando T, Taniguchi S, Ishii I, Tohya K, Ishizaki T, Niki I, Kimura T
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 442 Pages: 227-233

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distribution of hydrogen sulfide (H2S)-producing enzymes and the roles of the H)S donor sodium hydrosulfide in diabetic nephropathy.2013

    • Author(s)
      Yamamoto J, Sato W, Kosugi T, Yamamoto T, Kimura T, Taniguchi S, Kojima H, Maruyama S, Imai E, Matsuo S, Yuzawa Y, Niki I
    • Journal Title

      Clin Exp Nephrol.

      Volume: 17 Pages: 32-40

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distribution of hydrogen sulfide (H(2)S)-producing enzymes and the roles of the H(2)S donor sodium hydrosulfide in diabetic nephropathy.2012

    • Author(s)
      Yamamoto J
    • Journal Title

      Clin Exp Nephrol.

      Volume: 17(1) Issue: 1 Pages: 32-40

    • DOI

      10.1007/s10157-012-0670-y

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protein phosphorylation involved in the gene expression of the hydrogen sulphide producing enzyme cystathionine γ-lyase in the pancreatic β-cell2012

    • Author(s)
      Taniguchi S, Kimura T, Umeki T, Kimura Y, Kimura H, Ishii I, Itoh N, Naito Y, Yamamoto H, Niki I
    • Journal Title

      Mol.Cell.Endocrinol.

      Volume: 350 Issue: 1 Pages: 31-38

    • DOI

      10.1016/j.mce.2011.11.016

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protein phosphorylation involved in the gene expression of the hydrogen sulphide producing enzyme cystathionine γ-lyase in the pancreatic β-cell2012

    • Author(s)
      Taniguchi S, Kimura T, Umeki T, Kimura Y, Kimura H, Ishii I, Itoh N, Naito Y, Yamamoto H, Niki I
    • Journal Title

      Molecular and Cellular Endocrinology

      Volume: 350 Pages: 31-38

    • Related Report
      2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rab27a in pancreatic beta-cells, a busy protein in membrane trafficking2011

    • Author(s)
      Kimura T, Niki I
    • Journal Title

      Prog.Biophys.Mol.Biol.

      Volume: 107 Issue: 2 Pages: 219-223

    • DOI

      10.1016/j.pbiomolbio.2011.06.016

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rab27a, actin and beta-cell endocytosis [Review]2011

    • Author(s)
      Kimura T, Niki I
    • Journal Title

      Endocrine Journal

      Volume: 58 Issue: 1 Pages: 1-6

    • DOI

      10.1507/endocrj.K10E-391

    • NAID

      130004443655

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hydrogen sulphide protects mouse pancreatic beta-cells from cell death induced by oxidative stress, but not by endoplasmic reticulum stress2011

    • Author(s)
      Taniguchi S, Kang L, Kimura T, Niki I
    • Journal Title

      Brit. J. Pharmacol

      Volume: 162 Issue: 5 Pages: 1171-1178

    • DOI

      10.1111/j.1476-5381.2010.01119.x

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rab GTPases control membrane recycling in the pancreatic beta cell2011

    • Author(s)
      Kimura T, Niki I
    • Journal Title

      Beta Cells : Functions, Pathology and Research, Gallagher SE (ed.), Nova Biomedical, NY

      Pages: 123-130

    • URL

      https://www.novapublishers.com/catalog/product_info.php?cPath=23_131_162&products_id=12468

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rab27a in pancreatic beta-cells, a busy protein in membrane trafficking2011

    • Author(s)
      Kimura T, Niki I
    • Journal Title

      Progress in Biophysics and Molecular Biology

      Volume: 107 Pages: 219-223

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 内因性硫化水素は糖毒性から膵B細胞を保護することで2型糖尿病の発症を遅延させる.2014

    • Author(s)
      岡本光弘、山岡真美、安藤朋海、寺林健、武井真大、仁木一郎、石崎敏理、木村俊秀
    • Organizer
      第87回 日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] IQGAP1によるエンドサイトーシスの制御機構の解析2013

    • Author(s)
      木村俊秀
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2013-03-23
    • Related Report
      2013 Final Research Report
  • [Presentation] 硫化水素産生酵素欠損マウスと耐糖能異常.2013

    • Author(s)
      岡本光弘、山岡真美、武井真大、石井功、仁木一郎、木村俊秀
    • Organizer
      第56回 日本糖尿病学会年次総会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 硫化水素産生酵素欠損マウスと耐糖能異常.2013

    • Author(s)
      岡本光弘、山岡真美、武井真大、石崎敏理、石井功、仁木一郎、木村俊秀
    • Organizer
      第23回 日本病態生理学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Rab27a-GAP新規結合タンパク質の同定と膵B細胞における機能の解析.2013

    • Author(s)
      山岡真美、武井真大、岡本光弘、仁木一郎、石崎敏理、木村俊秀
    • Organizer
      第51回 日本糖尿病学会九州地方会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Annual Research Report
  • [Presentation] 誘導型硫化水素産生酵素CSEによる膵B細胞保護.2013

    • Author(s)
      木村俊秀
    • Organizer
      第24回 フォーラム イン ドージン
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 膵B細胞におけるRab27a-GAP新規結合タンパク質の機能解析.2013

    • Author(s)
      山岡真美、岡本光弘、武井真大、石崎敏理、仁木一郎、木村俊秀
    • Organizer
      第66回 日本薬理学会西南部会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] エンドサイトーシスの時間的制御機構の解析.2013

    • Author(s)
      木村俊秀
    • Organizer
      第2回 群馬大学生体調節研究所 内分泌・代謝学共同研究拠点シンポジウム
    • Place of Presentation
      群馬
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] IQGAP1によるエンドサイトーシスの制御機構の解析.2013

    • Author(s)
      木村俊秀、山岡真美、岡本光弘、武井真大、石崎玲、泉哲郎、仁木一郎
    • Organizer
      第86回 日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] The regulatory mechanism of intracellular localization of the GDP-dependent Rab27a effector coronin 3 in pancreatic beta-cells2012

    • Author(s)
      Toshihide Kimura
    • Organizer
      48th Annual meeting of European Association for the Study of Diabetes
    • Place of Presentation
      ベルリン,ドイツ
    • Year and Date
      2012-10-01
    • Related Report
      2013 Final Research Report
  • [Presentation] インスリン分泌時における膵B細胞の恒常性維持システムの解析2012

    • Author(s)
      木村俊秀
    • Organizer
      第22回日本病態生理学会
    • Place of Presentation
      大分
    • Year and Date
      2012-08-04
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] GDP型Rab27a新規結合タンパク質IQGAP1によるエンドサイトーシスの制御2012

    • Author(s)
      木村俊秀
    • Organizer
      第55回日本糖尿病学会
    • Place of Presentation
      横浜
    • Year and Date
      2012-05-17
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Rab27aとcoronin3の細胞内局在を規定する新規GDP依存性Rab27aエフェクターの同定2012

    • Author(s)
      木村俊秀
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Year and Date
      2012-03-16
    • Related Report
      2013 Final Research Report
  • [Presentation] The regulatory mechanism of intracellular localization of the GDP-dependent Rab27a effector coronin 3 in pancreatic beta-cells.2012

    • Author(s)
      Toshihide Kimura, Mami Yamaoka, Shigeki Taniguchi, Ichiro Niki
    • Organizer
      48th Annual meeting of European Association for the Study of Diabetes
    • Place of Presentation
      ドイツ
    • Related Report
      2012 Research-status Report
  • [Presentation] インスリン分泌時における膵B細胞の恒常性維持システムの解析.2012

    • Author(s)
      木村俊秀
    • Organizer
      第24回分子糖尿病学シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Rab27aとcoronin3の細胞内局在を規定する新規GDP依存性Rab27aエフェクターの同定2012

    • Author(s)
      木村俊秀、山岡真美、谷口繁生、仁木一郎
    • Organizer
      第85回 日本薬理学会
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] マウス膵B細胞における硫化水素産生酵素のカルシウム依存性発現調節2012

    • Author(s)
      谷口繁生、木村俊秀、岡本光弘、山本秀幸、仁木一郎
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] GDP型Rab27a結合タンパク質coronin3の細胞内局在を制御する機構の解析2011

    • Author(s)
      木村俊秀
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-15
    • Related Report
      2013 Final Research Report
  • [Presentation] インスリン顆粒膜のエンドサイトーシスを調節するGDP型Rab27aエフェクターによる分子クラスターの形成2011

    • Author(s)
      木村俊秀
    • Organizer
      第54回日本糖尿病学会
    • Place of Presentation
      北海道
    • Year and Date
      2011-05-19
    • Related Report
      2013 Final Research Report
  • [Presentation] インスリン顆粒膜のエンドサイトーシスを調節するGDP型Rab27aエフェクターによる分子クラスターの形成2011

    • Author(s)
      木村俊秀、山岡真美、谷口繁生、仁木一郎
    • Organizer
      第54回 日本糖尿病学会
    • Place of Presentation
      北海道
    • Related Report
      2011 Research-status Report
  • [Presentation] 硫化水素が膵B細胞を保護する分子機序の検討2011

    • Author(s)
      谷口繁生、康林、木村俊秀、仁木一郎
    • Organizer
      第54回 日本糖尿病学会
    • Place of Presentation
      北海道
    • Related Report
      2011 Research-status Report
  • [Presentation] Gタンパク質におけるGDP型依存性エフェクターの発見と膵B細胞での役割2011

    • Author(s)
      木村俊秀
    • Organizer
      群馬大学生体調節研究所 グローバルCOE特別セミナー(招待講演)
    • Place of Presentation
      群馬
    • Related Report
      2011 Research-status Report
  • [Presentation] 低分子量GTP結合タンパク質(Gタンパク質)におけるGDP依存性エフェクターの発見2011

    • Author(s)
      木村俊秀
    • Organizer
      第8回 九州先進糖尿病研究会(招待講演)
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report
  • [Presentation] GDP型Rab27aエフェクターによる分子クラスターの形成とエンドサイトーシスの制御2011

    • Author(s)
      木村俊秀、山岡真美、谷口繁生、仁木一郎
    • Organizer
      第64回 日本薬理学会西南部会
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report
  • [Presentation] 膵島における硫化水素産生酵素の発現調節の種差について2011

    • Author(s)
      谷口繁生、木村俊秀、岡本光弘、仁木一郎
    • Organizer
      第64回 日本薬理学会西南部会
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report
  • [Presentation] GDP型Rab27a結合タンパク質coronin3の細胞内局在を制御する機構の解析2011

    • Author(s)
      木村俊秀、山岡真美、谷口繁生、仁木一郎
    • Organizer
      第34回 日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] Rab27a-GAP新規結合タンパク質の探索2011

    • Author(s)
      山岡真美、木村俊秀、谷口繁生、仁木一郎
    • Organizer
      第34回 日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Book] GDP型Gタンパク質シグナリング生化学2013

    • Author(s)
      木村俊秀、山岡真美
    • Publisher
      日本生化学会
    • Related Report
      2013 Final Research Report
  • [Book] 硫化水素による膵B細胞保護DOJIN NEWS2013

    • Author(s)
      木村俊秀、岡本光弘
    • Publisher
      同仁化学研究所
    • Related Report
      2013 Final Research Report
  • [Book] 硫化水素と膵B細胞機能日本臨床2013

    • Author(s)
      岡本光弘、山岡真美、木村俊秀
    • Publisher
      日本臨床社
    • Related Report
      2013 Final Research Report
  • [Book] DOJIN NEWS2013

    • Author(s)
      木村俊秀、岡本光弘
    • Total Pages
      4
    • Publisher
      同仁化学研究所
    • Related Report
      2013 Annual Research Report
  • [Book] 生化学2013

    • Author(s)
      木村俊秀、山岡真美
    • Total Pages
      5
    • Publisher
      日本生化学会
    • Related Report
      2013 Annual Research Report
  • [Book] 日本臨床2013

    • Author(s)
      岡本光弘、山岡真美、木村俊秀
    • Total Pages
      6
    • Publisher
      日本臨床社
    • Related Report
      2012 Research-status Report
  • [Book] Rab27a-GAP新規結合タンパク質の同定とその機能解析、日本病態生理学会雑誌2012

    • Author(s)
      山岡真美、岡本光弘、仁木一郎、木村俊秀
    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www.med.oita-u.ac.jp/pharmacology/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 大分大学 医学部 薬理学講座

    • URL

      http://www.med.oita-u.ac.jp/pharmacology/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 大分大学薬理学講座

    • URL

      http://www.med.oita-u.ac.jp/pharmacology/

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.med.oita-u.ac.jp/pharmacology/index.html

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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