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Analysis of the regulation-mechanism of intracellular dynamics of late endosome and lysosome by using a FRET biosensor

Research Project

Project/Area Number 24657094
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionTokyo University of Science

Principal Investigator

NAKAMURA Takeshi  東京理科大学, 生命医科学研究所, 教授 (60362604)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsGタンパク質 / シグナル伝達 / 分解経路 / リソソーム / FRET / G蛋白質 / 後期エンドソーム / Rab7 / Rab5
Outline of Final Research Achievements

Rab7 is known to be a key molecule which regulates dynamics of lysosomes, in which a variety of biomolecules and damaged organelles are destructed. In this study, I have developed a FRET sensor, Raichu-Rab7, which can visualize the spatiotemporal change of Rab7 activity in living cells. Raichu-Rabs7 has shown the existence of a significant variation in Rab7 activity of individual endosomes in steady-state COS-7 cells. Next, I investigated the mechanism regulating Rab7 activity during the process from late endosomes to lysosomes in steady-state cells and macropinocytosis in EGF-stimulated COS-7 cells. Based on these studies, I have concluded that Rab7 on late endosomes is activated by Mon1/Ccz1 complex and plays an essential role in the fusion between late endosome and lysosome; on the contrary, Rab7 activation on lysosomes is independent of Mon1/Ccz1 and active Rab7 on lysosomes is implicated in the perinuclear accumulation of lysosomes.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (14 results)

All 2015 2014 2013 2012

All Journal Article (5 results) (of which Peer Reviewed: 3 results) Presentation (9 results) (of which Invited: 4 results)

  • [Journal Article] エクソサイトーシス2015

    • Author(s)
      中村岳史、七尾友久
    • Journal Title

      生体の科学

      Volume: 66

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Longest neurite-specific activation of Rap1B in hippocampal neurons contributes to polarity formation through RalA and Nore1A in addition to PI3-kinase.2013

    • Author(s)
      Nakamura T, Yasuda S, Nagai H, Koinuma S, Morishita S, Goto A, Kinashi T, Wada N.
    • Journal Title

      Genes Cells.

      Volume: 18(11) Issue: 11 Pages: 1020-31

    • DOI

      10.1111/gtc.12097

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] GTP hydrolysis of TC10 promotes neurite outgrowth through exocytic fusion of Rab11- and L1-containing vesicles by releasing exocyst component Exo70.2013

    • Author(s)
      2. Fujita, A., Koinuma, S., Yasuda, S., Nagai, H., Kamiguchi, H., Wada, N., and Nakamura, T.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 11 Pages: 9593-9601

    • DOI

      10.1371/journal.pone.0079689

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] All members of the EPI64 subfamily of TBC/RabGAPs also have GAP activities toward Ras2013

    • Author(s)
      Hiroyuki Nagai
    • Journal Title

      J. Biochem

      Volume: 153 Issue: 3 Pages: 283-288

    • DOI

      10.1093/jb/mvs147

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 化学とゲノム医学2013

    • Author(s)
      安田さや香、中村岳史
    • Journal Title

      化学と教育

      Volume: 61 Pages: 116-119

    • Related Report
      2012 Research-status Report
  • [Presentation] cAMPによる神経突起伸展におけるRhoファミリー分子TC10の役割と活性変化2014

    • Author(s)
      鯉沼真吾、藤田明音、安田さや香、和田直之、中村岳史
    • Organizer
      第37回分子生物学会年会
    • Place of Presentation
      横浜パシフィコ(神奈川県)
    • Year and Date
      2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of spatial change and temporal distribution of Rab35 activity during neurite outgrowth2014

    • Author(s)
      Hiroyuki Nagai, Nanako Ishido, Sayaka Yasuda, Hotaka Kobayashi, Mitsunori Fukuda, Takeshi Nakamura
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      横浜パシフィコ(神奈川県)
    • Year and Date
      2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 膜輸送を制御するシグナルの動態を可視化する2013

    • Author(s)
      1. 中村岳史
    • Organizer
      第8回スフィンゴテラピィ研究会
    • Place of Presentation
      石川
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] エンドソーム成熟とオートファジーに関わるRab7の活性可視化2013

    • Author(s)
      5. 安田さや香、大西悠希、藤田明音、川崎司人、和田直之、和栗聡、Giampietro Schiavo、福田光則、中村岳史
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] マクロピノサイトーシスにおけるRab5の活性制御の解析2012

    • Author(s)
      大西悠希、川崎司人 安田さや香、新井孝夫、中村岳史
    • Organizer
      日本バイオイメージング学会第21回大会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] マクロピノサイトーシスにおけるRab5の活性制御の解析2012

    • Author(s)
      安田さや香、川崎司人、大西悠希、中村岳史
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] A role of the Rac1-TC10 axis in neurite outgrowth2012

    • Author(s)
      Nakamura, T., Fujita, A., Matsuda, M, and Wada, N
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] A role of the Rac1-TC10 axis in neurite outgrowth2012

    • Author(s)
      Nakamura, T.
    • Organizer
      日米脳科学セミナー Growth cones and axon regeneration
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] RhoGTPaseによる細胞形態制御の数理モデル- 定量データと力の導入2012

    • Author(s)
      作村諭一、田中大河、池田和司、中村岳史
    • Organizer
      日本植物学会第76回大会
    • Place of Presentation
      姫路
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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