• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Regulation of retrograde transport mediated by LRRK1-Dynein complex

Research Project

Project/Area Number 15H04697
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionNagoya University

Principal Investigator

Hanafusa Hiroshi  名古屋大学, 理学研究科, 准教授 (00345844)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
KeywordsLRRK1 / EGFR / CLIP170 / Rab7 / 細胞内トラフィック / Dynein / オートファゴソーム / エンドソーム
Outline of Final Research Achievements

From this study, we revealed that (1) LRRK1 functions to initiate the transport of EGFR-containing endosom along microtubules through the phosphorylation of a microtubule plus end-binding factor CLIP-170 and the promotion of its binding to p150Glued. Furthermore, we revealed that (2) LRRK1 phosphorylates Ser-72 located in the SwitchII region of Rab7 and selectively promotes the binding between Rab7 and RILP. In addition, we revealed that (3) LRRK1 was activated in the M-phase centrosome and phosphorylates the centrosome component CDK5RAP2. This functions in the regulation of spindle orientation by promoting g-tubulin-dependent microtubule nucleation.

Academic Significance and Societal Importance of the Research Achievements

ある種の癌細胞では、EGFRシグナルが過剰になっている。我々はLRRK1が、EGFRの細胞内トラフィックを制御することで、EGFRシグナルを負に制御することを明らかにした。このことは、過剰なEGFRシグナルが引き起こす細胞癌化に対し、それを防ぐ手立てを開発するのに役立つ可能性がある。さらにLRRK1のファミリー分子LRRK2は、家族性パーキンソン病原因遺伝子(Park8)であるが、その作用機序や生理的役割・パーキンソン病発症機構は依然として不明なままである。LRRK1とLRRK2は一部共通の機構で機能しており、LRRK1の機能解析はLRRK2の作用機構解明に繋がる可能性がある。

Report

(4 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (7 results)

All 2019 2018 2017 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (5 results) (of which Invited: 3 results)

  • [Journal Article] LRRK1 phosphorylation of Rab7 at Ser-72 links trafficking of EGFR-containing endosomes to its effector RILP2019

    • Author(s)
      Hiroshi Hanafusa, Takuya Yagi, Haruka Ikeda, Naoki Hisamoto, Tomoki Nishioka, Kozo Kaibuchi, Kyoko Shirakabe, & Kunihiro Matsumoto
    • Journal Title

      Journal of Cell Science

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LRRK1-phosphorylated CLIP-170 regulates EGFR trafficking by recruiting p150Glued to microtubule plus ends2015

    • Author(s)
      Shin Kedashiro, Strahil I. Pastuhov, Tomoki Nishioka, Takashi Watanabe, Kozo Kaibuchi, Kunihiro Matsumoto, Hiroshi Hanafusa
    • Journal Title

      Journal of Cell Science

      Volume: 128 Pages: 385-96

    • DOI

      10.1242/jcs.161547

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] LRRK1によるエンドソームから発信されるEGFRシグナルの制御2018

    • Author(s)
      花房洋
    • Organizer
      日本生化学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ROCO family kinase LRRK1 regulates the transport and maturation of EGFR-containing endosomes2018

    • Author(s)
      花房洋
    • Organizer
      Annual Congress of Molecular & Cell Biology-2018
    • Related Report
      2017 Annual Research Report
  • [Presentation] LRRK1による細胞内トラフィックを介したEGFRシグナル制御2017

    • Author(s)
      花房洋
    • Organizer
      分子生物学会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ROCOファミリーキナーゼLRRK1による シリア退縮制御2016

    • Author(s)
      花房洋
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ROCO family kinase LRRK1 regulates the transport and maturation of autophagosomes through Rab7 phosphorylation2016

    • Author(s)
      花房洋
    • Organizer
      日本細胞生物学会
    • Place of Presentation
      京都
    • Year and Date
      2016-06-15
    • Related Report
      2015 Annual Research Report
    • Invited

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi