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Study on the novel degradation pathway from recycling endosomes to lysosomes

Research Project

Project/Area Number 24657125
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Cell biology
Research InstitutionTohoku University

Principal Investigator

FUKUDA Mitsunori  東北大学, 生命科学研究科, 教授 (50311361)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsリサイクリングエンドソーム / リソソーム / 蛋白質分解 / トランスフェリン受容体 / アミノ酸トランスポーター / Rab / 低分子量G蛋白質 / 膜輸送
Research Abstract

Small GTPase Rab12 has recently been suggested to regulate a new membrane traffic pathway form recycling endosomes to lysosomes to degrade recycling molecules, but its physiological significance remained unknown. In this study, we found that Rab12 promotes constitutive degradation of PAT4 (proton-coupled amino-acid transporter 4). Because PAT4 is involved in the uptake of amino acids from the extracellular medium, knockdown of Rab12 in MEF cells increased the intracellular concentration of L-amino acids, resulting in the activation of mTORC1 and inhibition of autophagy. Our findings suggest that Rab12 suppresses excessive cell growth by maintaining the proper amount of PAT4 at the plasma membrane.

Report

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

    (19 results)

All 2014 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 5 results) Presentation (11 results) (of which Invited: 3 results) Remarks (2 results)

  • [Journal Article] Slp2-a controls renal epithelial cell size through regulation of Rapezrin signaling independently of Rab272014

    • Author(s)
      Yasuda T, Fukuda M
    • Journal Title

      Joumal of Cell Science

      Volume: 127 Pages: 557-570

    • DOI

      10.1242/jcs.134056

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Methods of analyasis of the membrane trafficking pathway from recycling endosomes to lysosomes2013

    • Author(s)
      Matsui, T., Fukuda, M.
    • Journal Title

      Methods in Enzymology

      Volume: 534 Pages: 195-206

    • DOI

      10.1016/b978-0-12-397926-1.00011-1

    • ISBN
      9780123979261
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rab27 effectors, pleiotropic regulators in secretory pathways.2013

    • Author(s)
      Fukuda, M.
    • Journal Title

      Traffic

      Volume: 14 Issue: 9 Pages: 949-963

    • DOI

      10.1111/tra.12083

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4.2013

    • Author(s)
      Matsui, T. and Fukuda, M.
    • Journal Title

      EMBO Reports

      Volume: 14 Issue: 5 Pages: 450-457

    • DOI

      10.1038/embor.2013.32

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Rab interacting lysosomal protein (RILP)homology domain functions as a novel effector domain for small GTPase Rab36 : Rab36 regulates retrograde melanosome transport in melanocytes.2012

    • Author(s)
      Matsui, T., Ohbayashi, N. and Fukuda, M.
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 287 Issue: 34 Pages: 28619-28631

    • DOI

      10.1074/jbc.m112.370544

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] トランスフェリン受容体の恒常的分解を制御する低分子量GTPase Rab122012

    • Author(s)
      松井貴英、福田光則
    • Journal Title

      生体の科学

      Volume: 63(5) Pages: 512-513

    • URL

      http://www.igaku-shoin.co.jp/journalDetail.do?journal=34660

    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] アミノ酸トランスポーターの分解を介した新規栄養シグナルとオートファジーの制御機構2014

    • Author(s)
      松井貴英、福田光則
    • Organizer
      第119回日本解剖学会総会・全国学術集会シンポジウム「オルガネラの恒常性維持機構〜疾患を見据えた細胞生物学的アプローチ〜」
    • Place of Presentation
      栃木
    • Year and Date
      2014-03-27
    • Related Report
      2013 Final Research Report
  • [Presentation] Rab12はアミノ酸トランスポーターPAT4の分解制御を介してmTORC1とオートファジーを制御する2013

    • Author(s)
      松井貴英、福田光則
    • Organizer
      第7回オートファジー研究会
    • Place of Presentation
      掛川
    • Year and Date
      2013-12-19
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Dennd3はRab12の活性化を介してmTORC1活性及びオートファジーを調節する2013

    • Author(s)
      野口憲太、松井貴英、福田光則
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-03
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 低分子量GTPase Rab12によるリサイクリングエンドソームからリソソームへの新規分解経路の制御機構2013

    • Author(s)
      福田光則
    • Organizer
      第65回日本細胞生物学会大会シンポジウム「タンパク質分解システムによる細胞制御」
    • Place of Presentation
      名古屋
    • Year and Date
      2013-06-21
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Rab12はアミノ酸トランスポーターPAT4の分解制御を介してmTORC1とオートファジーを制御する2013

    • Author(s)
      松井貴英、福田光則
    • Organizer
      第65回日本細胞生物学会大会
    • Place of Presentation
      名古屋
    • Year and Date
      2013-06-20
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 低分子量GTPase Rabが司る多彩な生命現象~メラニン輸送、神経細胞の極性輸送からオートファジーまで~2012

    • Author(s)
      福田光則
    • Organizer
      理化学研究所・細胞システムコロキウム
    • Place of Presentation
      埼玉
    • Year and Date
      2012-12-07
    • Related Report
      2013 Final Research Report
  • [Presentation] Small GTPase Rab12 regulates constitutive degradation of transferrin receptor2012

    • Author(s)
      Takahide Matsui & Mitsunori Fukuda
    • Organizer
      Cold Spring Harbor Asia Conference"Small GTPase different scales : proteins, membranes, cells"
    • Place of Presentation
      Suzhou, China
    • Year and Date
      2012-09-25
    • Related Report
      2013 Final Research Report
  • [Presentation] Rab36はRILPとの結合を介してメラノソームの逆行性微小管輸送を制御する2012

    • Author(s)
      松井貴英、大林典彦、福田光則
    • Organizer
      第4回新学術領域研究「細胞内ロジスティクス」班会議
    • Place of Presentation
      秋保
    • Related Report
      2013 Final Research Report
  • [Presentation] アミノ酸トランスポーターの分解を介した新規栄養シグナルとオートファジーの制御機構

    • Author(s)
      松井貴英、福田光則
    • Organizer
      第119回日本解剖学会総会・全国学術集会シンポジウム「オルガネラの恒常性維持機構 -疾患を見据えた細胞生物学的アプローチ-」
    • Place of Presentation
      栃木
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] The Rab family small GTPases regulate membrane trafficking in melanocytes.

    • Author(s)
      Fukuda, M.
    • Organizer
      Cold Spring Harbor Asia Conference “Small GTPase different scales: proteins, membranes, cells”
    • Place of Presentation
      Suzhou, China
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 低分子量GTPase Rabが司る多彩な生命現象 ~メラニン輸送、神経細胞の極性輸送からオートファジーまで~

    • Author(s)
      福田光則
    • Organizer
      理化学研究所・細胞システムコロキウム
    • Place of Presentation
      埼玉
    • Related Report
      2012 Research-status Report
    • Invited
  • [Remarks] 東北大学・生命科学研究科・膜輸送機構解析分野・ホームページ

    • URL

      http://www.lifesci.tohoku.ac.jp/teacher/t_fukuda/

    • Related Report
      2013 Final Research Report
  • [Remarks] 東北大学大学院生命科学研究科

    • URL

      http://www.lifesci.tohoku.ac.jp/teacher/t_fukuda/

    • Related Report
      2013 Annual Research Report

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

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