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Molecular machinery of granule exocytosis in pancreatic α and β cells

Research Project

Project/Area Number 20390253
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionGunma University

Principal Investigator

IZUMI Tetsuro  Gunma University, 生体調節研究所, 教授 (00212952)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2010: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2009: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Keywords遺伝子 / 細胞・組織 / 生理学 / 蛋白質 / 糖尿病
Research Abstract

We have analyzed the functional significance of lipid and protein interactions involving the Rab27a effector, granuphilin, in both cultured cells and genetically engineered mice. We have also found that another Rab27a effector, exophilin8, transiently traps insulin granules into the cortical actin network close to the microtubule plus-ends and supplies them for release during the stimulation. Finally, using a proteomics approach, we have systemically identified Rab27a-interacting molecules in both α and β cells.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (57 results)

All 2011 2010 2009 2008 Other

All Journal Article (18 results) (of which Peer Reviewed: 17 results) Presentation (32 results) Book (5 results) Remarks (2 results)

  • [Journal Article] Exophilin8 transiently clusters insulin granules at the actin-rich cell cortex prior tc exocytosis.2011

    • Author(s)
      Mizuno K, Ramalho JS, Izumi T
    • Journal Title

      Mol.Biol.Cell (in press)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneous modes of insulin granule exocytosis : molecular determinants.2011

    • Author(s)
      Izumi T
    • Journal Title

      Front.Biosci. 16

      Pages: 360-367

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneous modes of insulin granule exocytosis : molecular determinants2011

    • Author(s)
      Izumi T
    • Journal Title

      Front.Biosci.

      Volume: 16 Pages: 360-367

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exophilin8 transiently clusters insulin granules at the actin-rich cell cortex prior to exocytosis.2011

    • Author(s)
      Mizuno K., et al
    • Journal Title

      Mol.Biol.Cell

      Volume: in press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autophagy requires endoplasmic reticulum targeting of the P13-kinase complex via Atg14L.2010

    • Author(s)
      Matsunaga K, Morita E, Saitoh T, Akira S, Ktistakis NT, Izumi T, Noda T, Yoshimori T
    • Journal Title

      J.Cell Biol. 190

      Pages: 511-521

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo gene delivery by cationic tetraamino fullerene. Proc.2010

    • Author(s)
      Maeda-Mamiya R, Norii E, Isobe H, Nakanishi W, Okamoto K, Doi K, Sugaya T, Izumi T, Homma T, Nakamura F
    • Journal Title

      Natl.Acad.Sci.USA 107

      Pages: 5339-5344

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo gene delivery by cationic tetraamino fullerene2010

    • Author(s)
      Maeda-Mamiya R., et al
    • Journal Title

      Proc.Natl.Acad.Sci.USA

      Volume: 107 Pages: 5339-5344

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L2010

    • Author(s)
      Matsunaga K., et al
    • Journal Title

      J.Cell Biol.

      Volume: 190 Pages: 511-521

    • Related Report
      2010 Annual Research Report
  • [Journal Article] In vivo gene delivery by cationic tetraamino fullerene In vivo gene delivery by cationic tetraamino fullerene2010

    • Author(s)
      Maeda-Mamiya R., et al
    • Journal Title

      Proc.Natl. Acad. Sci. USA 107

      Pages: 5339-5344

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Vps33a in the fusion of uroplakin-degrading multivesicular bodies with lysosomes.2009

    • Author(s)
      Guo X, Tu L, Gumper I, Plesken H, Novak EK, Chintala S, Swank RT, Pastores G, Torres P, Izumi T, Sun T-T, Sabatini DD, Kreibich G
    • Journal Title

      Traffic 10

      Pages: 1350-1361

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Vps33a in the fusion of uroplakin-degrading multivesicular bodies with lysosomes2009

    • Author(s)
      Guo X., et al
    • Journal Title

      Traffic 10

      Pages: 1350-1361

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elucidation of Rab27 recruitment by its effector : structure of Rab27a bound to Exophilin4/SIp2-a.2008

    • Author(s)
      Chavas LMG, Ihara K, Kawasaki M, Torii S, Ue j ima T, Kato R, I zumi T, Wakatsuki S
    • Journal Title

      Structure 16

      Pages: 1468-1477

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Purification, crystallization and preliminary X-ray crystallographic analysis of Rab27a GTPase in complex with exophilin4/SIp2-a effector.2008

    • Author(s)
      Chavas LMG, Ihara K, Kawasaki M, Kato R, Izumi T, Wakatsuki S
    • Journal Title

      Acta Crystallogr. Sect.F-Struct.Biol.Cryst.Commun. 64

      Pages: 599-601

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Docking is not a prerequisite but a temporal constraint for fusion of secretory granules.2008

    • Author(s)
      Kasai K, Fujita T, Gomi H, Izumi T
    • Journal Title

      Traffic 9

      Pages: 1191-1203

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Syntaxin 8 has two functionally distinct di-leucine-based motifs.2008

    • Author(s)
      Kasai K, Suga K, Izumi T, Akagawa K
    • Journal Title

      Cell.Mol.Biol.Lett. 13

      Pages: 144-154

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Docking is not a prerequisite but a temporal constraint for fusion of secretory granules2008

    • Author(s)
      Kasai K., et al
    • Journal Title

      Traffic 9

      Pages: 1191-1203

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Purification, crystallization and preliminary X-ray crystallographic analysis of Rab27a GTPase in complex with exophilin4/S1p2-a effector2008

    • Author(s)
      Chavas LMG., et al
    • Journal Title

      Acta Crystallogr. Sect. F. Biol. Cryst. Commun. 64

      Pages: 599-601

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elucidation of Rab27 recruitment by its effector: structure of Rab27a bound to Exonhilin4/SIn2-a2008

    • Author(s)
      Chavas LMG., et al
    • Journal Title

      Structure 16

      Pages: 1468-1477

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Mechanism for regulated exocytosis of insulin granules in pancreatic beta cells.2010

    • Author(s)
      Ray Ishizaki, Hao Wang, Jun Xu, Tetsuro Izumi
    • Organizer
      JSH (Japanese Society of Hematology) International Symposium 2010 in Akita : Seven Wonders of Erythropoiesis.
    • Place of Presentation
      Akita, Japan
    • Year and Date
      2010-07-17
    • Related Report
      2010 Final Research Report
  • [Presentation] Mechanism for regulated exocytosis of insulin granules in pancreatic beta cells2010

    • Author(s)
      Ray Ishizaki., et al
    • Organizer
      JSH (Japanese Society of Hematology) International Symposium 2010 in Akita
    • Place of Presentation
      秋田大学(秋田県)
    • Year and Date
      2010-07-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] インスリン分泌機構におけるRab27aエフェクターの役割2010

    • Author(s)
      泉哲郎、石崎玲、徐君、水野広一
    • Organizer
      文部科学省科学研究補助金「新学術領域研究(細胞内ロジスティクス)」第2回班会議
    • Place of Presentation
      札幌
    • Year and Date
      2010-07-01
    • Related Report
      2010 Final Research Report
  • [Presentation] Roles of Rab27a and its multiple effectors in insulin exocytosis.2010

    • Author(s)
      泉哲郎
    • Organizer
      (シンポジウム:膵β細胞研究の最前線(1)「インスリン分泌」)。第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山
    • Year and Date
      2010-05-28
    • Related Report
      2010 Final Research Report
  • [Presentation] Roles of Rab27a and its multiple effectors in insulin exocytosis2010

    • Author(s)
      泉哲郎
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山コンベンションセンター(岡山県)
    • Year and Date
      2010-05-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] Differential granule-targeting activities between two Rab27a effectors expressed in pancreatic β cells2010

    • Author(s)
      Hao Wang, Jun Xu, Ray Ishizaki, Tetsuro Izumi
    • Organizer
      14th International Congress of Endocrinology (ICE2010)
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2010-03-29
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular determinants of insulin granule exocytosis.2010

    • Author(s)
      泉哲郎
    • Organizer
      Workshop : Genesis and function of pancreatic β cells. The official satellite symposium "New insight into pathogenesis and treatment of diabetes" of the 14th international congress of endocrinology (ICE2010)
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2010-03-25
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular determinants of insulin granule exocytosis. Workshop : Genesis and function of pancreatic β cells2010

    • Author(s)
      泉哲郎
    • Organizer
      The official satellite symposium "New insight in to pathogenesis and treatment of diabetes" of the 14^<th> international congress of endocrinology (ICE2010)
    • Place of Presentation
      東京
    • Year and Date
      2010-03-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] Exophilin8を介したインシュリン穎粒の形質膜下アクチン網への移行は微小管プラス端近傍でおきている(ワークショップ:メンブレントラフィック(II)2010

    • Author(s)
      水野広一、泉哲郎
    • Organizer
      第62回日本細胞生物学会大会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] Exophilin8を介したインシュリン顆粒の形質膜下アクチン網への移行は微小管プラス端近傍でおきている2010

    • Author(s)
      水野広一、泉哲郎
    • Organizer
      第62回日本細胞生物学会大会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Differential granule-targeting activities between two Rab27a effectors expressed in pancreatic β cells2010

    • Author(s)
      Hao Wang, 徐君, et al
    • Organizer
      14^<th> International Congress of Endocrinology (ICE2010)
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] 調節性分泌の分子機序と内分泌代謝性疾患の発症・病態への関与2009

    • Author(s)
      泉哲郎、水野広一、王昊、石崎玲
    • Organizer
      新学術領域研究「細胞内ロジスティクス」班会議
    • Place of Presentation
      名護
    • Year and Date
      2009-11-10
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 分泌穎粒開口放出の分子機序2009

    • Author(s)
      泉哲郎
    • Organizer
      第8回肺サーファクタント分子病態研究会「肺における細胞内輸送と病態生理」
    • Place of Presentation
      札幌(特別講演)
    • Year and Date
      2009-06-27
    • Related Report
      2010 Final Research Report
  • [Presentation] 分泌顆粒開口放出の分子機序(特別講演)2009

    • Author(s)
      泉哲郎
    • Organizer
      第8回肺サーファクタント分子病態研究会「肺における細胞内輸送と病態生理」
    • Place of Presentation
      札幌
    • Year and Date
      2009-06-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] Roles of multiple Rab27a effectors expressed in pancreatic beta cells.2009

    • Author(s)
      Tetsuro Izumi, Jun Xu, Hao Wang, Koichi Mizuno, Hiroshi Gomi, Ray Ishizaki.
    • Organizer
      Gunma University & Akita University International Symposium of Global COE Program : New aspects in immunology and cancer research
    • Place of Presentation
      Akita, Japan
    • Year and Date
      2009-06-24
    • Related Report
      2010 Final Research Report
  • [Presentation] 膵β細胞に発現する2つのRab27エフェクターの機能差異2009

    • Author(s)
      石崎玲、徐君、泉哲郎
    • Organizer
      第52回日本糖尿病学会年次学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2009-05-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 膵β細胞に発現する2つのRab27エフェクターの機能差異2009

    • Author(s)
      石崎玲、徐君、泉哲郎
    • Organizer
      第82回日本内分泌学会学術総会
    • Place of Presentation
      前橋
    • Year and Date
      2009-04-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 細胞膜マイクロドメイン-ラフトを介したインスリン分泌過程の解明2009

    • Author(s)
      笠井篤子、泉哲郎
    • Organizer
      第82回日本内分泌学会学術総会
    • Place of Presentation
      前橋
    • Year and Date
      2009-04-23
    • Related Report
      2010 Final Research Report
  • [Presentation] インスリン穎粒の細胞膜開口放出に関わる因子(β細胞の最前線)2009

    • Author(s)
      泉哲郎
    • Organizer
      第43回糖尿病学の進歩
    • Place of Presentation
      松本
    • Year and Date
      2009-02-20
    • Related Report
      2010 Final Research Report
  • [Presentation] 分泌穎粒開口放出の仕組み2009

    • Author(s)
      泉哲郎
    • Organizer
      特定領域研究「メンブレントラフィック」終了・新学術領域研究「ロジスティクス」発足合同シンポジウム:メンブレントラフィックから細胞内ロジスティクスへ
    • Place of Presentation
      東京
    • Year and Date
      2009-01-29
    • Related Report
      2010 Final Research Report
  • [Presentation] 細胞膜マイクロドメイン-ラフトを介したインスリン分泌過程の解明2009

    • Author(s)
      笠井篤子、泉哲郎
    • Organizer
      第82回日本分泌学会学術総会
    • Place of Presentation
      前橋
    • Related Report
      2009 Annual Research Report
  • [Presentation] 膵β細胞に発現する2つのRab27エフェクターの機能差異2009

    • Author(s)
      石崎玲、徐君、泉哲郎
    • Organizer
      第82回日本分泌学会学術総会
    • Place of Presentation
      前橋
    • Related Report
      2009 Annual Research Report
  • [Presentation] Roles of multiple Rab27a effectors expressed in pancreatic beta cells2009

    • Author(s)
      泉哲郎, 他
    • Organizer
      Gunma University & Akita University International Symposium of Global COE Program : New aspects in immunology and cancer research
    • Place of Presentation
      秋田
    • Related Report
      2009 Annual Research Report
  • [Presentation] Differential exocytic roles of Rab27a effectors expressed in pancreatic beta cells.2008

    • Author(s)
      Tetsuro Izumi, Jun Xu.
    • Organizer
      The 4th Scientific Meeting of Asia-Pacific Diabetes and Obesity Study Group
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2008-08-24
    • Related Report
      2010 Final Research Report
  • [Presentation] インスリン分泌穎粒の開口放出動態におけるRab27a/granuphilinの機能(ワークショップ:Rab蛋白質の高次機能)2008

    • Author(s)
      泉哲郎、河西和雄、藤田卓二、五味浩司
    • Organizer
      第60回日本細胞生物学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2008-06-30
    • Related Report
      2010 Final Research Report
  • [Presentation] Docking is not a prerequisite but a temporal constraint for fusion of secretory granules : roles of Rab27a/granuphilin on insulin exocytosis.2008

    • Author(s)
      Tetsuro Izumi, Kazuo Kasai, Takuji Fujita, Hiroshi Gomi.
    • Organizer
      2008 Keystone Symposium : Islet and Beta Cell Biology
    • Place of Presentation
      Snowbird, Utah, USA
    • Year and Date
      2008-04-08
    • Related Report
      2010 Final Research Report
  • [Presentation] インスリン穎粒の細胞膜ドッキングと開口放出(シンポジウム:インスリン分泌機構はどこまで解明されたのか)2008

    • Author(s)
      泉哲郎
    • Organizer
      第51回日本糖尿病学会年次学術、集会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] インスリン分泌穎粒の開口放出におけるRab27aおよびそのエフェクターGranuphilinの役割2008

    • Author(s)
      藤田卓二、五味浩司、泉哲郎
    • Organizer
      第51回日本糖尿病学会年次学術集会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] Docking is not a prerequisite but a temporal constraint for fusion of secretory granules: roles of Rab27a/granuphilin on insulin exocytosis2008

    • Author(s)
      Tetsuro Izumi
    • Organizer
      2008 Keystone Symposyum: Islet and Beta Cell Biolonv
    • Place of Presentation
      Snowbird,Utah,USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] インスリン顆粒の細胞膜ドッキングと開口放出(シンポジウム:インスリン分泌機構はどこまで解明されたのか)2008

    • Author(s)
      泉哲郎
    • Organizer
      第51回日本糖尿病学会年次学術集会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] インスリン分泌顆粒の開口放出動態におけるRab27a/Granuphilinの機能(ワークショップ:Rab蛋白sitsuno高次機能2008

    • Author(s)
      泉哲郎他
    • Organizer
      第60回日本細胞生物学会大会
    • Place of Presentation
      横浜
    • Related Report
      2008 Annual Research Report
  • [Presentation] Differencial exocytic roles of Rab27a effectors expressed in pancreatic beta cells2008

    • Author(s)
      Tetsuro Izumi,
    • Organizer
      The 4th scientific Meeting of Asia-Pacific Diabetes and Obesity Study Groun
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Book] 「新時代の糖尿病学(1)-病因・診断・治療研究の進歩-」日本臨床(インスリン開口分泌のメカニズム)2008

    • Author(s)
      泉哲郎
    • Publisher
      日本臨床社
    • Related Report
      2010 Final Research Report
  • [Book] 「メンブレントラフィックの奔流-分子から細胞、個体へ」蛋白質 核酸 酵素(インスリン分泌の分子メカニズム)2008

    • Author(s)
      泉哲郎
    • Publisher
      共立出版株式会社
    • Related Report
      2010 Final Research Report
  • [Book] インスリン開口分泌のメカニズム.「新時代の糖尿病学(1)一病因・診断・治療研究の進歩一」2008

    • Author(s)
      泉哲郎
    • Publisher
      日本臨床社
    • Related Report
      2008 Annual Research Report
  • [Book] インスリン分泌の分子メカニズム.「メンブレントラフィックの奔流一分子から細胞、個体へ」蛋白質核酸酵素2008

    • Author(s)
      泉哲郎
    • Publisher
      共立出版株式会社
    • Related Report
      2008 Annual Research Report
  • [Book] グラニュフィリン発見の体験記.「私の発見体験記〜成功と失敗のはざまで〜」実験医学262008

    • Author(s)
      泉哲郎
    • Publisher
      羊土社
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.imcr.gunma-u.ac.jp/lab/molend/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.imcr.gunma-u.ac.jp/lab/molend/

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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