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Mechanical properties of microtubule motors and the mechanisms of mitosis

Research Project

Project/Area Number 16H06166
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Biophysics
Research InstitutionNational Institute of Genetics

Principal Investigator

Shimamoto Yuta  国立遺伝学研究所, 遺伝メカニズム研究系, 准教授 (80409656)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
Keywords有糸分裂 / 微小管 / 分子モーター / 染色体分配 / 紡錘体 / メカニクス / キネシン / ダイニン / 力計測 / アフリカツメガエル / 真核細胞 / 細胞骨格 / キネシン5 / 多分子特性 / 光ピンセット / 一分子イメージング / 生物物理学
Outline of Final Research Achievements

We used a combination of biophysical force measurement, high-resolution imaging, biochemical perturbation, and materials science methods to elucidate the physical and molecular basis underlying the assembly of the metaphase spindle - the eukaryotic chromosome segregation machinery. We find that the spindle has a substantial mechanical heterogenity along the axis to which chromosomes are segregated, and the heterogeneity is linked to two key microtubule-based motors, kinesin-5 and dynein (Takagi et al., Dev Cell 2019). Our data propose how the spindle exerts relevant forces for chromosome segregation while adapting to perturbations for error-free cell division. We have also developed a method to prepare a frozen stock of Xenopus egg extracts with retained spindle assembly activity (Takagi et al., Mol Biol Cell 2019). Together, our study should help advance our understanding of spindle micromechanics in a variety of cellular contexts, such as those during embryonic development.

Academic Significance and Societal Importance of the Research Achievements

有糸分裂・減数分裂期における母細胞から娘細胞への遺伝情報の継承は、紡錘体と呼ばれるミクロンサイズの生体装置によって行われる。紡錘体に生じる欠陥はガンや不妊症と密接に関連する。本研究は、紡錘体が細胞内で正確に形成し機能を果たすしくみの一端を、その主骨格である微小管と、微小管を組み上げるモータータンパク質に着眼することで明らかにしたものである。本研究の成果は、紡錘体が自らのサイズを柔軟に調節しながら染色体を安定に分配するための物理的基礎と分子基盤を示唆するものであり、この細胞装置の動作原理の定量的理解に根ざした新たな疾患治療戦略の創出が期待される。

Report

(4 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (20 results)

All 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Open Access: 5 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 7 results,  Invited: 7 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] Academia Sinica(台湾)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Mechanically distinct microtubule arrays determine the length and force response of the meiotic spindle2019

    • Author(s)
      Jun Takagi, Ryota Sakamoto, Gen Shiratsuchi, Yusuke T. Maeda, Yuta Shimamoto
    • Journal Title

      Developmental Cell

      Volume: 49 Issue: 2 Pages: 267-278

    • DOI

      10.1016/j.devcel.2019.03.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analyzing the micromechanics of the cell division apparatus2018

    • Author(s)
      Yuta Shimamoto, Tarun M. Kapoor
    • Journal Title

      Methods in Cell Biology

      Volume: 145 Pages: 173-190

    • DOI

      10.1016/bs.mcb.2018.03.022

    • Related Report
      2018 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Endoplasmic Reticulum-Mediated Microtubule Alignment Governs Cytoplasmic Streaming2017

    • Author(s)
      Kenji Kimura, Alexandre Mamane, Tohru Sasaki, Kohta Sato, Jun Takagi, Ritsuya Niwayama, Lars Hufnagel, Yuta Shimamoto, Jean-Francois Joanny, Seiichi Uchida, and Akatsuki Kimura
    • Journal Title

      Nature Cell Biology

      Volume: 19 Issue: 4 Pages: 399-406

    • DOI

      10.1038/ncb3490

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] High-quality frozen extracts of Xenopus laevis eggs reveal size-dependent control of metaphase spindle micromechanics2017

    • Author(s)
      Takagi Jun、Shimamoto Yuta
    • Journal Title

      Molecular Biology of the Cell

      Volume: 28 Issue: 16 Pages: 2170-2177

    • DOI

      10.1091/mbc.e17-03-0174

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of mitotic spindle assembly factor NuMA by Importin-β2017

    • Author(s)
      Chang Chih-Chia、Huang Tzu-Lun、Shimamoto Yuta、Tsai Su-Yi、Hsia Kuo-Chiang
    • Journal Title

      The Journal of Cell Biology

      Volume: 216 Issue: 11 Pages: 3453-3462

    • DOI

      10.1083/jcb.201705168

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High quality frozen extracts of Xenopus laevis eggs reveal size-dependent control of metaphase spindle micromechanics2017

    • Author(s)
      Jun Takagi, Yuta Shimamoto
    • Journal Title

      bioRxiv

      Volume: n/a Pages: 112334-112334

    • DOI

      10.1101/112334

    • Related Report
      2016 Annual Research Report
    • Open Access / Acknowledgement Compliant
  • [Presentation] Examining the meiotic spindle micromechanics using cell-free extracts and quantitative micromanipulation2019

    • Author(s)
      Yuta Shimamoto
    • Organizer
      Japanese Biochemical Society 92nd Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Probing the local mechanical architecture of the vertebrate metaphase spindle2019

    • Author(s)
      Yuta Shimamoto
    • Organizer
      American Society for Cell Biology 2019 Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 紡錘体の構築原理と力学デザイン2019

    • Author(s)
      島本勇太
    • Organizer
      第37 回 染色体ワークショップ
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] In-situ force assay reveals mechanical heterogeneity and roles of parallel microtubule arrays in governing meiotic spindle length2018

    • Author(s)
      Jun Takagi, Yuta Shimamoto
    • Organizer
      American Society for Cell Biology 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] in-vitro再構成とin-situ計測が明らかにするメソスケールの紡錘体メカニクス2018

    • Author(s)
      島本勇太
    • Organizer
      第8回分子モーター討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mechanical design principles of the cell division apparatus2018

    • Author(s)
      Yuta Shimamoto
    • Organizer
      日本生物物理学会第56回年会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Probing the local mechanical architecture of the metaphase meiotic spindle2018

    • Author(s)
      Yuta Shimamoto
    • Organizer
      17th International Xenopus Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Micromanipulating the spindle to study chromosome segregation in anaphase2018

    • Author(s)
      Jun Takagi, Takeshi Itabashi, Shin’ichi Ishiwata, Yuta Shimamoto
    • Organizer
      Biophysical Society 62nd Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 有糸分裂モーターキネシン5の協同的な力発生と紡錘体サイズ制御のメカニズム2017

    • Author(s)
      島本勇太
    • Organizer
      日本細胞生物学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 有糸分裂紡錘体の集合と機能メカニクス2017

    • Author(s)
      島本勇太
    • Organizer
      細胞を創る研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Preparing frozen Xenopus egg extracts for the study of spindle assembly mechanisms2017

    • Author(s)
      Jun Takagi, Yuta Shimamoto
    • Organizer
      American Society for Cell Biology 2017 Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] アフリカツメガエル卵抽出液の冷凍保存方法及び冷凍保存用キット、アフリカツメガエル卵濃縮抽出液、並びに細胞周期の分析方法2018

    • Inventor(s)
      島本勇太、高木順
    • Industrial Property Rights Holder
      島本勇太、高木順
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2017 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] アフリカツメガエル卵抽出液の冷凍保存方法及び冷凍保存用キット、アフリカツメガエル卵濃縮抽出液、並びに細胞周期の分析方法2017

    • Inventor(s)
      島本勇太、高木潤
    • Industrial Property Rights Holder
      大学共同利用機関法人情報・システム研究機構
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-01-30
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2022-08-05  

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