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Functional analyses of small GTPase Rab proteins and their novel guanine nucleotide exchange factors

Research Project

Project/Area Number 17H03669
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionGunma University

Principal Investigator

Sato Ken  群馬大学, 生体調節研究所, 教授 (30311343)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords低分子量GTPase / GDP/GTP交換因子 / エンドサイトーシス / Rab / エンドソーム / 低分子量GTPase Rab / 細胞内膜交通 / メンブレントラフィック / 細胞・組織
Outline of Final Research Achievements

Rab11, which is a small GTPase, is localized in the Golgi apparatus and endosomes, and plays important roles such as endocytic recycling of cell membrane proteins and cell migration. Rab11 is also suggested to be associated with serious diseases such as ovarian cancer and breast cancer. In this study, we first clarified the molecular mechanism by which the Rab11 GDP / GTP exchange factor, REI-1 / SH3BP5 family, activates Rab11 by crystal structure analysis. In addition, we performed functional analysis of SH3BP5 and SH3BP5L in cultured mammalian cells and found that they localized to recycling endosomes and regulate cell migration by controlling intracellular trafficking of integrins.

Academic Significance and Societal Importance of the Research Achievements

本研究によって,既知のRab GDP/GTP交換因子とは異なるアミノ酸配列を持つREI-1/SH3BP5ファミリータンパク質がどのようにしてRab11を活性化するのか明らかとなった.この発見は60種以上存在するRabタンパク質の活性化機構に新たな知見を与えるものであり、学術的意義が高いと言える。また,これらの因子がRab11の活性化を通じてガン細胞等の細胞移動を制御していることが明らかとなった.Rab11は生物にとって必須であり阻害することは困難であるが,REI-1/SH3BP5タンパク質はRab11が関連するガン等の治療薬開発の新たな標的分子となる可能性があり、社会的にも意義があると言える.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (19 results)

All 2019 2018 2017

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (12 results) (of which Invited: 1 results)

  • [Journal Article] Synthesis and maintenance of lipid droplets are essential for mouse preimplantation embryonic development2019

    • Author(s)
      Aizawa Ryutaro、Ibayashi Megumi、Tatsumi Takayuki、Yamamoto Atsushi、Kokubo Toshiaki、Miyasaka Naoyuki、Sato Ken、Ikeda Shuntaro、Minami Naojiro、Tsukamoto Satoshi
    • Journal Title

      Development

      Volume: 146 Issue: 22

    • DOI

      10.1242/dev.181925

    • NAID

      120006876601

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis of guanine nucleotide exchange for Rab11 by SH3BP52019

    • Author(s)
      Goto-Ito Sakurako、Morooka Nobukatsu、Yamagata Atsushi、Sato Yusuke、Sato Ken、Fukai Shuya
    • Journal Title

      Life Science Alliance

      Volume: 2 Issue: 2 Pages: e201900297-e201900297

    • DOI

      10.26508/lsa.201900297

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rer1-mediated quality control system is required for neural stem cell maintenance during cerebral cortex development2018

    • Author(s)
      Taichi Hara, Ikuko Maejima, Tomoko Akuzawa, Rika Hirai, Hisae Kobayashi, Satoshi Tsukamoto, Mika Tsunoda, Aguri Ono, Shota Yamakoshi, Satoshi Oikawa and Ken Sato
    • Journal Title

      PLoS Genetics

      Volume: 14(9) Issue: 9 Pages: e1007647-e1007647

    • DOI

      10.1371/journal.pgen.1007647

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mutations in COA7 cause spinocerebellar ataxia with axonal neuropathy2018

    • Author(s)
      Higuchi Yujiro、Ohtake Akira、Matsuura Eiji、Ueda Takehiro、Toda Tatsushi、Yamashita Sumimasa、Yamada Kenichiro、Koide Takashi、Yaguchi Hiroaki、Mitsui Jun、Ishiura Hiroyuki、Yoshimura Jun、Doi Koichiro、Morishita Shinichi、Sato Ken、Nakagawa Masanori、Yamaguchi Masamitsu、Tsuji Shoji、Takashima Hiroshi
    • Journal Title

      Brain

      Volume: 印刷中 Issue: 6 Pages: 1622-1636

    • DOI

      10.1093/brain/awy104

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The autophagy receptor ALLO-1 and the IKKE-1 kinase control clearance of paternal mitochondria in Caenorhabditis elegans.2018

    • Author(s)
      M. Sato, K. Sato, K. Tomura, H. Kosako and K. Sato
    • Journal Title

      Nature Cell Biology

      Volume: 20 Issue: 1 Pages: 81-91

    • DOI

      10.1038/s41556-017-0008-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple ways to prevent transmission of paternal mitochondrial DNA for maternal inheritance in animals2017

    • Author(s)
      Sato Ken、Sato Miyuki
    • Journal Title

      The Journal of Biochemistry

      Volume: 162 Pages: 247-253

    • DOI

      10.1093/jb/mvx052

    • NAID

      40021380498

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Monitoring of Paternal Mitochondrial Degradation in Caenorhabditis elegans2017

    • Author(s)
      Sato Miyuki、Sato Ken
    • Journal Title

      Methods in Moleculra Biology

      Volume: Mitophagy Pages: 1-8

    • DOI

      10.1007/7651_2017_17

    • ISBN
      9781493977499, 9781493977505
    • Related Report
      2017 Annual Research Report
  • [Presentation] リポタンパク質の分泌を制御する SFT-4/Surf4 ファミリータンパク質の発見とその機能解析2019

    • Author(s)
      三枝慶子,佐藤美由紀,諸岡信克,原太一,佐藤健
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 初期発生における細胞内オルガネラリモデリング機構2019

    • Author(s)
      佐藤健
    • Organizer
      第66回日本実験動物学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 低分子量GTPase Rab35の生理機能解析2019

    • Author(s)
      前島郁子,古泉博之,阿久澤共子,平井里香,小林久江,磯部いの八,榎本和生,原太一,佐藤健
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 低分子量GTPase Rab11特異的な新規GEFであるSH3BP5/SH3BP5Lの哺乳類細胞における生理機能解析2019

    • Author(s)
      諸岡信克、佐藤美由紀、佐藤健
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 哺乳動物個体における低分子量GTPase Rab35の機能解析 Physiological analysis of mammalian small GTPase Rab352018

    • Author(s)
      前島郁子,古泉博之,阿久澤共子,平井里香,小林久江,磯部いの八,榎本和生,原太一,佐藤健
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The autophagy receptor ALLO-1 and the TBK1/IKKε-related kinase regulate clearance of paternal mitochondria in C. elegans2018

    • Author(s)
      Miyuki Sato, Ken Sato
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] キナーゼとアダプターによる父性オルガネラ選択的オートファジーの制御2018

    • Author(s)
      佐藤美由紀,佐藤健
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 低分子量GTPase Rab11に対する新規GDP/GTP交換因子(GEF)であるSH3BP5およびSH3BP5Lの哺乳類細胞における生理機能の解析2018

    • Author(s)
      諸岡信克、佐藤美由紀、佐藤健
    • Organizer
      日本農芸化学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] オートファジーによる父性オルガネラ選択的分解の分子メカニズム2018

    • Author(s)
      佐藤美由紀,佐藤健
    • Organizer
      第123回日本解剖学会全国学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 低分子量GTPase Rab11に対する新規GEF SH3BP5/SH3BP5Lの哺乳類における生理機能解析2017

    • Author(s)
      諸岡信克、佐藤美由紀、佐藤健
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The mechanism of paternal mitochondria clearance via allophagy2017

    • Author(s)
      Miyuki Sato, Katsuya Sato, Kotone Tomura, Hidetaka Kosako, and Ken Sato
    • Organizer
      The 8th International Symposium on Autophagy
    • Related Report
      2017 Annual Research Report
  • [Presentation] 父性オルガネラ選択的オートファジーにおける基質認識のメカニズム2017

    • Author(s)
      佐藤美由紀,佐藤克哉,戸村琴音,佐藤健
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2024-12-25  

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