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Molecular mechanism of insulin granules exocytosis via the novel Exophilin-8 complexes.

Research Project

Project/Area Number 15K08295
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionGunma University

Principal Investigator

Matsunaga Kohichi  群馬大学, 生体調節研究所, 助教 (20570162)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsインスリン / Rab27 / Exophilin / インスリン分泌 / Rab27a / メンブレントラフィック
Outline of Final Research Achievements

Insulin is produced by beta-cells and is stored as secretory granules in beta-cells of the pancreatic islets. Secretion of insulin requires a series of membrane dynamics, namely, producing granules from the Golgi apparatus, sorting to granules and maturation, and trafficking and fusion to the plasma membrane. Secretory granules transfer to the actin cortex near the plasma membrane before they fuse with plasma membrane. In the present study, we showed that Exophilin-8-knockout mice showed significantly higher blood glucose level, and Exophilin-8-null pancreatic beta-cells exhibited decreased insulin secretion in glucose stimulation and lost insulin granule location at the F-actin rich cell periphery. Furthermore, we found that Exophilin-8 formed the complex with RIM-BP2 and Myosin-VIIa, and the complex had important role for the granule localization to F-actin rich cell periphery.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (4 results)

All 2018 2017 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Exophilin-8 assembles secretory granules for exocytosis in the actin cortex via interaction with RIM-BP2 and myosin-VIIa2017

    • Author(s)
      Fan Fushun、Matsunaga Kohichi、Wang Hao、Ishizaki Ray、Kobayashi Eri、Kiyonari Hiroshi、Mukumoto Yoshiko、Okunishi Katsuhide、Izumi Tetsuro
    • Journal Title

      eLife

      Volume: 6 Pages: 1-23

    • DOI

      10.7554/elife.26174

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Rab27エフェクター、Exophilin-8/MyRIP/Slac2cのインスリン分泌における役割2018

    • Author(s)
      松永耕一、范福順、王昊、石崎玲、小林絵梨、清成寛、椋本淑子、奥西勝秀、泉哲郎
    • Organizer
      第70回日本細胞生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Rab27エフェクターExophilin8ノックアウトマウスのインスリン分泌制御における解析2016

    • Author(s)
      范福順、松永耕一、泉哲郎
    • Organizer
      日本糖尿病・肥満動物学会
    • Place of Presentation
      大宮ソニックシティビル
    • Year and Date
      2016-03-11
    • Related Report
      2015 Research-status Report
  • [Presentation] インスリン分泌制御におけるExophilin8たんぱく質の機能解析2015

    • Author(s)
      范福順、松永耕一、泉哲郎
    • Organizer
      北関東医学会
    • Place of Presentation
      群馬大学刀城会館
    • Year and Date
      2015-10-01
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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