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Is Rab11 involved in non-vesicular transport of cholesterol?

Research Project

Project/Area Number 16K15171
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General anatomy (including histology/embryology)
Research InstitutionOsaka University

Principal Investigator

Harada Akihiro  大阪大学, 医学系研究科, 教授 (40251441)

Research Collaborator YOSHIMURA Shin-ichiro  大阪大学, 医学系研究科細胞生物学教室, 講師
SOBAJIMA Tomoaki  大阪大学, 医学系研究科保健学専攻機能診断科学講座, 大学院生
MIYOSHI Eichi  大阪大学, 医学系研究科保健学専攻機能診断科学講座, 教授
MAEDA Tomomi  大阪大学, 医学系研究科保健学専攻機能診断科学講座, 大学院生
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsRELCH / Rab11 / リサイクリングエンドソーム / TGN / OSBP / 極性輸送 / コレステロール / 脂質 / 小胞輸送
Outline of Final Research Achievements

Cholesterol is one of major constituent of plasma membrane lipids. Though it is physiologically very important, the route of its transport remains largely elusive. We identified RELCH as a novel binding protein of Rab11. RELCH, Rab11, and OSBP makes a complex which transfer cholesterol from the recycling endosome (RE) to the TGN by bridging between the RE and the TGN without using vesicular trafficking mechanism. This result was published in the Journal of Cell Biology and selected as one of the best article in 2018.

Academic Significance and Societal Importance of the Research Achievements

我々は小胞輸送を司ると考えられてきたタンパク質Rab11の新規結合タンパク質RELCHを同定し、それが介する新規の輸送経路を明らかにした。この研究により、コレステロールの新たな輸送経路や分子機構が解明され、コレステロールの細胞内動態の全容解明の一端が明らかとなったため、これからの生命科学の発展に重要な役割を果たすと期待される。また、RELCHを欠損するマウスでは、肝臓や繊維芽細胞においてリソソームの増加やその中のコレステロールの増加がみられるため、脂肪肝やそれに起因する肝炎(NASH)の病態の解明に有用と考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 2016 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 6 results) Remarks (1 results)

  • [Journal Article] A Novel Contact by a Novel Protein Complex Supports Cholesterol Transport to the Endoplasmic Reticulum2018

    • Author(s)
      Harada Akihiro
    • Journal Title

      Contact

      Volume: 1 Pages: 77968-77968

    • DOI

      10.1177/2515256418779685

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Rab11-binding protein RELCH/KIAA1468 controls intracellular cholesterol distribution.2018

    • Author(s)
      Sobajima T., Yoshimura S*., Maeda T., Miyata H., Miyoshi E., and Harada A*. (*共同責任著者)
    • Journal Title

      J Cell Biol

      Volume: pii: jcb.201709123 Issue: 5 Pages: 1-15

    • DOI

      10.1083/jcb.201709123

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The molecular mechanism of cell polarity in various cell types2018

    • Author(s)
      Akihiro Harada
    • Organizer
      細胞生物、発生生物合同大会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of Rab11 in apical transport and non-vesicular cholesterol transport.2018

    • Author(s)
      Akihiro Harada
    • Organizer
      FASEB conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel contact by a novel protein complex supports cholesterol transport from the recycling endosome to the trans-Golgi network2018

    • Author(s)
      Akihiro Harada
    • Organizer
      FEBS Golgi meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The molecular mechanism of apical transport in the mouse intestinal epithelial cells: The role of Rabs and their binding proteins2017

    • Author(s)
      Akihiro Harada
    • Organizer
      EMBO conference ‘Cell polarity and membrane dynamics’ June 6, 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Rab11a GTPase regulates apical protein localization and microvilli formation in the intestine.2017

    • Author(s)
      Sobajima,Tomoaki, Shin-ichiro Yoshimura and Akihiro Harada
    • Organizer
      Gordon Research Conference
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Roles of Rab8, 10, and 11 for apical transport, ciliogenesis, and microvillus inclusion disease.2016

    • Author(s)
      原田彰宏
    • Organizer
      FASEB conference ‘GTPases in Trafficking, Autophagy and Disease’
    • Place of Presentation
      West Palm Beach, Florida, United States
    • Year and Date
      2016-09-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 大阪大学大学院 医学系研究科 細胞生物学

    • URL

      http://www.med.osaka-u.ac.jp/pub/acb/

    • Related Report
      2018 Annual Research Report 2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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