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モーター超分子複合体の分子構築と運動制御機構の解明

Publicly Offered Research

Project AreaHarmonized supramolecular machinery for motility and its diversity
Project/Area Number 25117503
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

豊島 陽子  東京大学, 総合文化研究科, 教授 (40158043)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywordsダイニン / ダイナクチン / 超分子複合体 / 金ナノ粒子 / p150 / CC1 / アンテナ構造 / 運動制御機構 / 金ナノ粒子標識 / 電子顕微鏡
Outline of Annual Research Achievements

ダイニンもダイナクチンも、ともに巨大で複雑な構造をもつ超分子複合体であるが、それらの構造と両者の相互作用については明らかでないことが多い。本研究では、ヒトHEK細胞で発現した組換え体ダイニンと組換え体ダイナクチンについて、金ナノ粒子を部位特異的に標識し、電子顕微鏡で観察してサブユニットの位置関係を明らかにした。特に、ダイニンの尾部構造中の中間鎖、中間軽鎖、軽鎖の位置を特定した結果、従来想定されていたサブユニットの配向と順序が逆であることがわかった。また、ダイナクチンのサイドアームにヘッドから突出する繊維状構造(アンテナ)があることを発見した。このアンテナ部分は、ダイニン結合部位であることが知られているp150のCC1領域であると同定した。CC1はコイルドコイルの二量体が中央付近で折れ曲がり、逆並行の4量体を形成していることが示唆された。
このCC1部位の断片を作製して、ダイニンに対する影響を調べたところ、本来、ダイニンの運動連続性を高めると考えられているダイナクチンの効果とは逆に、ダイニンと微小管の親和性を弱めて、ダイニンを微小管から引き剥がす効果があることが見出された。この効果は、ダイナクチンp150のバリアントのうち、K-richドメインをもたないダイナクチン1Bについても見られることから、ダイナクチン複合体がもつ本質的な生理作用であることが示唆された。このことから、ダイナクチンは1AにみられるK-richドメインによる微小管への親和性の増加と、CC1ドメインによるダイニンの微小管への親和性の低下の、両方の側面をもつ複雑なレギュレーターであることがわかった。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (25 results)

All 2014 2013

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) (of which Invited: 3 results)

  • [Journal Article] Autoinhibition and cooperative activation mechanisms of cytoplasmic dynein2014

    • Author(s)
      Torisawa, T., Ichikawa, M., Furuta, A., Saito, K., Oiwa, K., Kojima, H., Toyoshima, Y. Y. and Furuta, K.
    • Journal Title

      Nature Cell Biol

      Volume: 16 Issue: 11 Pages: 1118-1118

    • DOI

      10.1038/ncb3048

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Structure of the entire stalk region of the dynein motor domain2014

    • Author(s)
      Yosuke Nishikawa, Takuji Oyama, Narutoshi Kamiya, Takahide Kon, Yoko Y. Toyoshima, Haruki Nakamura, Genji Kurisu
    • Journal Title

      Journal of Molecular Biology

      Volume: 426 Issue: 19 Pages: 3232-3245

    • DOI

      10.1016/j.jmb.2014.06.023

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] バイオイメージングと光ピンセットを用いた微小管系モータータンパク質の協働的活性化に関する働き2014

    • Author(s)
      古田健也、鳥澤嵩征、豊島陽子
    • Journal Title

      生化学

      Volume: 86 Pages: 184-191

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sea lily muscle lacks a troponin-regulatory system but contains paramyosin.2014

    • Author(s)
      Obinata T, Amemiya S, Takai R, Ichikawa M, Toyosima YY, Sato N
    • Journal Title

      Zoological Science

      Volume: 31 Issue: 3 Pages: 122-128

    • DOI

      10.2108/zsj.31.122

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formation of Ring-Shaped Microtubule Assemblies through Active Self-Organization on Dynein2013

    • Author(s)
      Masaki Ito, Arif Md Rashedul Kabir, Daisuke Inoue, Takayuki Torisawa, Yoko Toyoshima, Kazuki Sada, Akira Kakugo
    • Journal Title

      Polymer Journal

      Volume: 46 Issue: 4 Pages: 220-225

    • DOI

      10.1038/pj.2013.89

    • NAID

      120005515308

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Measuring Collective Transport by Defined Numbers of Processive and Nonprocessive Kinesin Motors2013

    • Author(s)
      古田 健也, 古田 茜, 豊島 陽子, 網野 美紗子, 大岩 和弘, 小嶋 寛明
    • Journal Title

      Proc Natl Acad Sci U S A ( 米国科学アカデミー紀要)

      Volume: 110(2) Issue: 2 Pages: 501-6

    • DOI

      10.1073/pnas.1201390110

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Regulation of dynein motility by the antenna structure of dynactin p1502014

    • Author(s)
      T. Kobayashi, T. Miyashita, H. Kajita, K. Saito, T. Murayama, Y.Y. Toyoshima
    • Organizer
      The 2014 ASCB/IFCB Meeting
    • Place of Presentation
      Philadelphia, Pennsylvania, USA
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Antenna structure of dynactin complex2014

    • Author(s)
      Hatsuha Kajita, Takuya Kobayashi, Kei Saito, Yoko Y. Toyoshima
    • Organizer
      第52回日本生物物理学会年会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2014-09-13 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] A novel role of dynactin for dynein motility revealed by gliding assay2014

    • Author(s)
      Takuya Kobayashi, Hatsuha Kajita, Kei Saito, Yoko Y. Toyoshima
    • Organizer
      第52回日本生物物理学会年会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2014-09-13 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] A novel role of dynactin for dynein motility revealed by single-molecule assay2014

    • Author(s)
      Takuya Miyashita, Takuya Kobayashi, Hatsuha Kajita, Yoko Y. Toyoshima
    • Organizer
      第52回日本生物物理学会年会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2014-09-13 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Autoinhibiton and cooperative activation mechanisms of cytoplasmic dynein.2014

    • Author(s)
      Takayuki Torisawa, Ken’ya Furuta, Muneyoshi Ichikawa, Akane Furuta, Kei Saito, Kazuhiro Oiwa, Hiroaki Kojima, Yoko Toyoshima
    • Organizer
      第52回日本生物物理学会年会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2014-09-13 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cytoplasmic dynein takes a route switching randomly between protofilaments with a bias toward the right2014

    • Author(s)
      Mitsuhiro Sugawa, Shin Yamaguchi, Keitaro Shibata, Yoko Y. Toyoshima, Junichiro Yajima
    • Organizer
      第52回日本生物物理学会年会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2014-09-13 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Self-regulation of cytoplasmic dynein through its unconventional force response.2014

    • Author(s)
      Takayuki Torisawa, Ken’ya Furuta, Akane Furuta, Muneyoshi Ichikawa, Kei Saito, Kazuhiro Oiwa, Hiroaki Kojima, Yoko Toyoshima
    • Organizer
      Biophysical Society 58th Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] New Folding Pattern of p150 and “antenna” for dynein binding2014

    • Author(s)
      Kei Saito, Takashi Murayama, Tomonori Hata, Takuya Kobayashi, Yoko Toyoshima
    • Organizer
      Biophysical Society 58th Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Shin Yamaguchi, Kei Saito, Miki Sutoh, Takayuki Nishizaka, Yoko Y Toyoshima, Junichiro Yajima,2014

    • Author(s)
      Shin Yamaguchi, Kei Saito, Miki Sutoh, Takayuki Nishizaka, Yoko Y Toyoshima, Junichiro Yajima,
    • Organizer
      Biophysical Society 58th Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Autoinhibition and synergistid activation of cytoplasmic dynein2013

    • Author(s)
      Takayuki Torisawa, Ken’ya Furuta, Akane Furuta, Muneyoshi Ichikawa, Yoko Toyoshima
    • Organizer
      日本生物物理学会第51回年会
    • Place of Presentation
      京都府、京都国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] Regulatory mechanism of mictrotubule –based molecular motors by Bicaudal-D22013

    • Author(s)
      Takuya Kobayashi, Akira Hanashima, Yoko Toyoshima, Takashi Murayama
    • Organizer
      日本生物物理学会第51回年会
    • Place of Presentation
      京都府、京都国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular architecture of dynactin p1502013

    • Author(s)
      Kei Saito, Takashi Murayama, Tomonori Hata, Yoko Toyoshima
    • Organizer
      日本生物物理学会第51回年会
    • Place of Presentation
      京都府、京都国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] Subunit structure of Tetrahymena outer dynein arm complex2013

    • Author(s)
      Muneyoshi IMuneyoshi Ichikawa, Yasuharu Kushida, Kentaro Nakano, Osamu Numata, Yoko Toyoshima
    • Organizer
      日本生物物理学会第51回年会
    • Place of Presentation
      京都府、京都国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] The mechanism of determining the directionality of Ncd2013

    • Author(s)
      Masahiko Yamagishi, Yoko Toyoshima, Junichiro Yajima
    • Organizer
      日本生物物理学会第51回年会
    • Place of Presentation
      京都府、京都国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] Submolecular structure of cytoplasmic dynein tail and dynactin sidearm.2013

    • Author(s)
      Kei Saito, Yuta Watahabe, Muneyoshi Ichikawa, Tomonori Hata, Takuya Kobayashi, Takashi Murayama, Yoko Toyoshima
    • Organizer
      International Workshop Dynein2013
    • Place of Presentation
      兵庫県、神戸オルビスホール
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Torque generation by axonemal outer-arm dynein2013

    • Author(s)
      Shin Yamaguchi, Yoko Toyoshima, Junichiro Yajima
    • Organizer
      International Workshop Dynein2013
    • Place of Presentation
      兵庫県、神戸オルビスホール
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Self-regulation of cytoplasmic dynein2013

    • Author(s)
      Ken’ya Furuta, Takayuyki Torisawa, Akane Furuta, Muneyoshi Ichikawa, Kei Saito, Kazuhiro Oiwa, Hiroaki Kojima, Yoko Toyoshima
    • Organizer
      International Workshop Dynein2013
    • Place of Presentation
      兵庫県、神戸オルビスホール
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Self-regulation of cytoplasmic dynein2013

    • Author(s)
      Ken'ya Furuta, Takayuki Torisawa, Akane Furuta, Muneyoshi Ichikawa, Kei Saito, Kauzuhiro Oiwa, Hiroaki Kojima, Yoko Toyoshima
    • Organizer
      American Society for Cell Biology 2013 Annual Meeting
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Submolecular structure of dynactin sidearm: a new folding pattern of p1502013

    • Author(s)
      Kei Saito, Tomonori Hata, Takuya Kobayashi, Takashi Murayama, Yoko Toyoshima
    • Organizer
      American Society for Cell Biology 2013 Annual Meeting
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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