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Role of protein conformational dynamics and disorder regions in the regulation of the actin cytoskeleton

Research Project

Project/Area Number 21K06838
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionThe University of Tokushima

Principal Investigator

SAKANE Ayuko  徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (60509777)

Co-Investigator(Kenkyū-buntansha) 佐々木 卓也  徳島大学, 大学院医歯薬学研究部(医学域), 教授 (40241278)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアクチン細胞骨格制御 / 蛋白質の構造ダイナミクス / Disorder領域
Outline of Research at the Start

細胞の運動、接着、形態形成等の細胞機能では、アクチン細胞骨格がダイナミックに制御されている。これまで、研究代表者は、マルチドメイン蛋白質であるJunctional Rab13-binding protein (JRAB)の1分子構造ダイナミクスがアクチン細胞骨格の時空間制御に関わることを明らかにしてきた。近年、蛋白質の構造において安定的な構造を形成しないdisorder領域の機能が注目を集めており、本研究では、JRABが有するdisorder領域の新規役割を構造変化と関連付けて明らかにすることを目指す。

Outline of Final Research Achievements

We have previously shown that the single molecule conformational dynamics of the multi-domain protein, Junctional Rab13-binding protein (JRAB), is involved in the spatiotemporal regulation of the actin cytoskeleton. Recently, the function of the disorder region, which does not form a stable structure in the protein structure, has attracted much attention. JRAB also has an extensive disorder region between the N- and C-termini, involvement of the region in functional expression is expected. Therefore, in this study, we attempted to elucidate the multifaceted regulatory mechanism of the actin cytoskeleton in terms of dynamics of JRAB and JRAB-JRAB binding protein complexes and novel roles of the disorder region.

Academic Significance and Societal Importance of the Research Achievements

本研究では、細胞の運動、接着、形態形成等の細胞機能においてJRABあるいはJRABとその結合蛋白質群との複合体の構造ダイナミクスが、如何にしてアクチン細胞骨格を多面的に制御するのかを明らかにすることを目的とした。近年、蛋白質の構造において安定的な構造を形成しないdisorder領域の機能が注目されているが、本研究では、JRABが有するdisorder領域がその本体であることを明らかにした点に学術的意義がある。得られた成果が蛋白質複合体による細胞機能の制御機構の破綻によって引き起こされる疾患の病態の解明に繋がることも十分予想され、医学・医療分野への大きな波及効果が期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (4 results)

All 2023 2022 2021

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

  • [Journal Article] Rapid, high-sensitivity detection of biomolecules using dual-comb biosensing2023

    • Author(s)
      Miyamura Shogo、Oe Ryo、Nakahara Takuya、Koresawa Hidenori、Okada Shota、Taue Shuji、Tokizane Yu、Minamikawa Takeo、Yano Taka-Aki、Otsuka Kunihiro、Sakane Ayuko、Sasaki Takuya、Yasutomo Koji、Kajisa Taira、Yasui Takeshi
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 14541-14541

    • DOI

      10.1038/s41598-023-41436-3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] s-Afadin binds to MAGUIN/Cnksr2 and regulates the localization of the AMPA receptor and glutamatergic synaptic response in hippocampal neurons2023

    • Author(s)
      Maruo Tomohiko、Mizutani Kiyohito、Miyata Muneaki、Kuriu Toshihiko、Sakakibara Shotaro、Takahashi Hatena、Kida Daichi、Maesaka Kouki、Sugaya Tsukiko、Sakane Ayuko、Sasaki Takuya、Takai Yoshimi、Mandai Kenji
    • Journal Title

      Journal of Biological Chemistry

      Volume: 299(4) Issue: 4 Pages: 103040-103040

    • DOI

      10.1016/j.jbc.2023.103040

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] JRAB/MICAL-L2 undergoes liquid-liquid phase separation to form tubular recycling endosomes2021

    • Author(s)
      Sakane Ayuko、Yano Taka-aki、Uchihashi Takayuki、Horikawa Kazuki、Hara Yusuke、Imoto Issei、Kurisu Shusaku、Yamada Hiroshi、Takei Kohji、Sasaki Takuya
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 551-551

    • DOI

      10.1038/s42003-021-02080-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The role and significance of JRAB/MICAL-L2-mediated molecular complex formation and dissociation in the regulation of membrane structure and function2022

    • Author(s)
      坂根亜由子、佐々木卓也
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
    • Invited

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Published: 2021-04-28   Modified: 2025-01-30  

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