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2012 Fiscal Year Final Research Report

Molecular mechanism of regulated exocytosis and its involvement in endocrine and metabolic diseases

Planned Research

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Project AreaIntracellular logistics: interdisciplinary approaches to pathophysiology of membrane traffic
Project/Area Number 20113005
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionGunma University

Principal Investigator

IZUMI Tetsuro  群馬大学, 生体調節研究所, 教授 (00212952)

Project Period (FY) 2008 – 2012
Keywords分泌穎粒 / 調節性分泌 / 開口放出 / 糖尿病 / 内分泌 / Rabタンパク質
Research Abstract

We aimed to identify molecular mechanism and functional significance of granule docking to the plasma membrane in regulated exocytosis. For this purpose, we first analyzed the function of the Rab27 effector granuphilin and its partner, syntaxin-la, using gene-knockout mice. We found that only granuphilin, but not syntaxin-la, is essential for the docking process. We also established the microscopic system to simultaneously observe behavior of granules and associated molecules in living cells to explore the relationship between granule docking and fusion. Furthermore, we discovered the roles of other Rab27 effectors in regulated exocytosis: exiphilin7 functions in the exocytosis of undocked granules, whereas exophilin8 is involved in the recruitment of granules into the cortical actin network.

  • Research Products

    (32 results)

All 2013 2012 2011 2010 2009 2008 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (17 results) Remarks (1 results)

  • [Journal Article] The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane2013

    • Author(s)
      Wang H, Ishizaki R, Xu J, Kasai K, Kobayashi E, Gomi H, Izumi T
    • Journal Title

      Mol. Biol. Cell

      Volume: 24 Pages: 319-330

    • Peer Reviewed
  • [Journal Article] Activin receptor-like kinase 7 suppresses lipolysis to accumulate fat in obesity through downregulation of peroxisonle proliferator-activated receptor γ and C/EBPα2013

    • Author(s)
      Yogosawa S, Mizutani S, Ogawa Y, and Izunli T
    • Journal Title

      Diabetes

      Volume: 62 Pages: 115-123

    • Peer Reviewed
  • [Journal Article] Adipose cell and lipid turnovers in obesity and insulin resistance2012

    • Author(s)
      Izumi T
    • Journal Title

      Diabetol. Int

      Volume: 3 Pages: 184-186

    • Peer Reviewed
  • [Journal Article] Modular genetic control of sexually dimorphic behaviors2012

    • Author(s)
      Xu X, Coats JK, Yang CF, Wang A, Ahmed OM, Alvarado M, Izumi T, and Shah NM
    • Journal Title

      Cell

      Volume: 148 Pages: 596-607

    • Peer Reviewed
  • [Journal Article] Loss of granuphilin and loss of syntaxin-la cause differential effects on insulin granule docking and fusion2011

    • Author(s)
      Wang H, Ishizaki R, Kobayashi E, Fujiwara T, Akagawa K, and Izumi T
    • Journal Title

      J. Biol. Chem

      Volume: 286 Pages: 32244-32250

    • Peer Reviewed
  • [Journal Article] Exophilin8 transiently clusters insulin granules at the actin-rich cell cortex prior to exocytosis2011

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

      Mol. Biol. Cell

      Volume: 22 Pages: 1716-1726

    • 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

    • Peer Reviewed
  • [Journal Article] Autophagy requires endoplasmic reticulum targeting of the Pl3-inase complex via Atg14L2010

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

      J. Cell Biol

      Volume: 190 Pages: 511-521

    • Peer Reviewed
  • [Journal Article] In vivo gene delivery by cationic tetraamino fullerene2010

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

      Proc. Natl. Acad. Sci. USA

      Volume: 107 Pages: 5339-5344

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

    • 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, and Kreibich G
    • Journal Title

      Traffic

      Volume: 10 Pages: 1350-136

    • Peer Reviewed
  • [Journal Article] Elucidation of Rab27 recruitement by its effector: structure of Rab27a bound to Exophilin4/Slp2-a2008

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

      Structure

      Volume: 16 Pages: 1468-1477

    • Peer Reviewed
  • [Journal Article] Purification, crystallization and preliminary X-ray crystallographic analysis of Rab27a GTPase in complex with exophilin4/Slp2-a effector2008

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

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

      Volume: 64 Pages: 599-601

    • Peer Reviewed
  • [Journal Article] Syntaxin 8 has two functionally distinct di-leucine-based motifs2008

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

      Cell. Mol. Biol. Lett

      Volume: 13 Pages: 144-154

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

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

      Traffic

      Volume: 9 Pages: 1191-1203

    • Peer Reviewed
  • [Presentation] Exophilin7 promotes fusion of undocked granule in Pancreatic β cells2012

    • Author(s)
      Ray Ishizaki, Hao Wang, Jun Xu, and Tetsuro Izumi
    • Organizer
      Joint Meeting of The 45th Annual Meeting of the Japanese Biology
    • Place of Presentation
      Kobe International Conference Center, Kobe, Japan
    • Year and Date
      20120528-29
  • [Presentation] The Rab27a effector exophilin7 promotes fusion of insulin granules without stable docking to the plasma nlenlbrane2012

    • Author(s)
      Hao Wang, Ray Ishizaki, Jun Xu, Kazuo Kasai, Hiroshi Gomi, and Tetsuro Izumi
    • Organizer
      9th International Diabetes Federation Western Pacific Region Congress / 4th Scientific Meeting ofthe Asian Association for the Study of Diabetes
    • Place of Presentation
      Kyoto International Conference Center, Kyoto, Japan
    • Year and Date
      2012-11-27
  • [Presentation] 膵β細胞に発現するRab27aエフェクターExophilin7遺伝子欠損マウスの解析2012

    • Author(s)
      石崎 玲、王 昊、泉 哲郎
    • Organizer
      平成24年度日本生化学会関東支部例会
    • Place of Presentation
      群馬大学.前橋
    • Year and Date
      2012-06-23
  • [Presentation] 膵β細胞に発現するRab27エフェクターExophilin7遺伝子欠損マウスの解析2012

    • Author(s)
      王 昊.石崎 玲.徐 君.泉 哲郎
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      パシフィコ横浜.横浜
    • Year and Date
      2012-05-19
  • [Presentation] Roles of multiple Rab27a effectors in insulin granule exocytosis.(シンポジウム:2型糖尿病 インスリン分泌)2012

    • Author(s)
      泉 哲郎
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      パシフィコ横浜.横浜
    • Year and Date
      2012-05-17
  • [Presentation] GranuphilinとSyntaxin-1a二重欠損マウスを用いたイ ンスリン分泌機構の解析2012

    • Author(s)
      王 昊.石崎 玲.泉 哲郎.藤原智徳.赤川 公朗
    • Organizer
      第26回日本糖尿病・肥満動物学会年次学術集会
    • Place of Presentation
      愛知県産業労働センター.名古屋
    • Year and Date
      2012-02-17
  • [Presentation] Loss of granuphilin and of syntaxin-la cause differential effectson insulin granule docking and fusion2011

    • Author(s)
      Hao Wang, Ray Ishizaki, Tomonori Fujiwara, Kumio Akagawa, and Tetsuro Izumi
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜.横浜
    • Year and Date
      2011-12-15
  • [Presentation] GranuphilinとSyntaxin-la二重欠損マウスを用いたインスリン分泌機構の解析2011

    • Author(s)
      石崎 玲.王 昊.藤原 智徳.赤川公朗.泉 哲郎
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館.京都
    • Year and Date
      2011-09-22
  • [Presentation] Mechanism for regulated exocytosis of insulin granules in pancreatic beta cells (Japanese Society of Hematology)2010

    • Author(s)
      Ray Ishizaki, Hao Wang, Jun Xu, and Tetsuro Izumi
    • Organizer
      International Symposium 2010 in Akita : Seven Wonders of Erythropoiesis
    • Place of Presentation
      Akita University, Akita, Japan
    • Year and Date
      20100716-17
  • [Presentation] Roles of Rab27a and its multiple effectors in insulin exocytosis.(シンポジウム:膵β細胞研究の最前線(1)「インスリン分泌」)2010

    • 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
    • Year and Date
      20100527-29
  • [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
      大阪国際会議場.大阪
    • Year and Date
      20100519-21
  • [Presentation] Differential granule-targeting activities between two Rab27a effectors expressed in Pancreaticβcells2010

    • Author(s)
      Hao Wang, Jun Xu, Ray Ishizaki, and Tetsuro Izumi
    • Organizer
      14th International Congress of Endocrinology (ICE2010)
    • Place of Presentation
      Kyoto International Conference Center, Kyoto, Japan
    • Year and Date
      20100326-30
  • [Presentation] Molecular deternlinants of insulin granule exocytosis. Workshop: Genesis and function of pancreaticβcells2010

    • Author(s)
      Tetsuro Izunli
    • Organizer
      The official satellite symposium "New insight into pathogenesis and treatment of diabetes" of the 14th international congress of endocrinology (ICE2010)
    • Place of Presentation
      Tokyo Conference Center Shinagawa, Tokyo, Japan
    • Year and Date
      2010-03-25
  • [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
      ホテルNCB,大阪国際会議場.大阪
    • Year and Date
      20090521-24
  • [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
      群馬県民会館,前橋商工会議所.前橋
    • Year and Date
      20090423-25
  • [Presentation] 細胞膜マイクロドメインー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
      群馬県民会館,前橋商工会議所.前橋
    • Year and Date
      20090423-25
  • [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
      長野県松本文化会館,まつもと市民芸術館.松本
    • Year and Date
      20090220-21
  • [Remarks]

    • URL

      http://molend.showa.gunma-u.ac.jp

URL: 

Published: 2014-08-29  

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