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Spatiotemporal control system of spindle function by photoreactive kinesin

Research Project

Project/Area Number 20K15744
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionThe University of Tokyo

Principal Investigator

Yamagishi Masahiko  東京大学, 大学院総合文化研究科, 助教 (30815501)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords分子モーター / キネシン / 光制御 / モータータンパク質
Outline of Research at the Start

真核細胞に共通する細胞分裂装置である紡錘体の機能を解明するためには、紡錘体の構成要素であるモータータンパク質がいつ・どこで「力仕事」をするかを調べる必要がある。本研究では、光応答性タンパク質の構造変化を利用して、光照射により標的キネシンの運動機能のON/OFFを制御し、紡錘体形成におけるキネシンの活性を分裂中の特定時期や限られた場所で制御できるシステムを構築し、キネシンの時空間的分子プロセスを明らかにすることを目的とする。

Outline of Final Research Achievements

To elucidate the functionality of the spindle apparatus, a universal cellular motility apparatus in eukaryotic cells, it is necessary to determine when and where motor proteins are active. This study aims to investigate the activity of motor proteins involved in spindle formation at specific times and locations by introducing light-responsive proteins into the motor proteins and constructing an experimental system to control their motility through light irradiation.
Initially, the motility functions of individual motor proteins, namely kinesin-1, kinesin-5, and kinesin-14, were elucidated through in vitro experiments, identifying the parts involved in torque generation and directional control. Additionally, the introduction sites of light-responsive proteins that do not hinder motility were examined, and mutant variants with surface residue substitutions were created and evaluated.

Academic Significance and Societal Importance of the Research Achievements

紡錘体の機能解明は生物学や医学分野において重要です。細胞分裂の異常はがんや発達異常の原因となるため、紡錘体の正常な機能の理解は疾患予防や治療法の開発につながります。光制御技術を応用すると、特定の時期や場所でタンパク質の活性を制御する手法の開発が期待されます。本研究では紡錘体のモータータンパク質の活性化時期と位置を明らかにし、その機能や制御メカニズムに新たな知見をもたらすことができます。さらに、キネシンの個別の運動機能解明は細胞内の運動プロセスの理解を深める上で重要です。これらの成果は学術的に価値があり、紡錘体の機能解明による社会的な利益や疾患の予防・治療に寄与する可能性があります。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (7 results)

All 2023 2022 2021 2020

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (3 results)

  • [Journal Article] Torque generating properties of Tetrahymena ciliary three-headed outer-arm dynein2022

    • Author(s)
      Yamaguchi Shin、Yamagishi Masahiko、Yajima Junichiro
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 16722-16722

    • DOI

      10.1038/s41598-022-21001-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anchoring geometry is a significant factor in determining the direction of kinesin-14 motility on microtubules2022

    • Author(s)
      Yamagishi Masahiko、Sumiyoshi Rieko、Drummond Douglas R.、Yajima Junichiro
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 15417-15417

    • DOI

      10.1038/s41598-022-19589-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of the motility of monomeric kinesin-5/Cin82021

    • Author(s)
      Yamagishi Masahiko、Maruyama Yohei、Sugawa Mitsuhiro、Yajima Junichiro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 555 Pages: 115-120

    • DOI

      10.1016/j.bbrc.2021.03.134

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] N‐terminal β‐strand of single‐headed kinesin‐1 can modulate the off‐axis force‐generation and resultant rotation pitch2020

    • Author(s)
      Yamagishi Masahiko、Fujimura Shoko、Sugawa Mitsuhiro、Nishizaka Takayuki、Yajima Junichiro
    • Journal Title

      Cytoskeleton

      Volume: 77 Issue: 9 Pages: 351-361

    • DOI

      10.1002/cm.21630

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 何がキネシンを一方向に運動させるのか?2023

    • Author(s)
      山岸 雅彦
    • Organizer
      THE ToKYo Molecular Motor Show
    • Related Report
      2022 Annual Research Report
  • [Presentation] Plus-end directionality is present in the catalytic core of kinesin-14 minus-end directed motors2021

    • Author(s)
      Masahiko Yamagishi, Junichiro Yajima
    • Organizer
      第59回生物物理学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] The N-terminal β-strand of single-headed kinesin-1 is involved in the off-axis force-generation and resultant rotation pitch2020

    • Author(s)
      Masahiko Yamagishi, Shoko Fujimura, Mitsuhiro Sugawa, Takayuki Nishizaka, Junichiro Yajima
    • Organizer
      第58回生物物理学会年会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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