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2008 Fiscal Year Final Research Report

Creation of Mechanobiology Based on Mechanosensitive Channels

Research Project

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Project/Area Number 16GS0308
Research Category

Grant-in-Aid for Creative Scientific Research

Allocation TypeSingle-year Grants
Research InstitutionNagoya University

Principal Investigator

SOKABE Masahiro  Nagoya University, 大学院・医学系研究科, 教授 (10093428)

Co-Investigator(Kenkyū-buntansha) TATSUMI Hitoshi  名古屋大学, 大学院・医学系研究科, 准教授 (20171720)
Co-Investigator(Renkei-kenkyūsha) NARUSE Keiji  岡山大学, 大学院・医歯薬学総合研究科, 教授 (40252233)
YOSHIMURA Kenjiro  筑波大学, 大学院・生命環境科学科, 教授 (10230806)
Project Period (FY) 2004 – 2008
Keywordsメカノバイオロジー / 細菌SAチャネル / メカノセンサー / 細胞骨格 / チャネルブロッカー / 蜘蛛毒 / 接着斑 / 心房細動
Research Abstract

細胞の機械刺激受容・応答能は生命現象を支える根幹機能であるが、その分子機構は全く未解明であった。本研究では、(1)変異体を用いた実験とシミュレーションにより、機械刺激受容チャネルである細菌Mscの張力感知部位を同定し、活性化過程における膜脂質との相互作用・張力感知とチャネル開閉の連関の詳細を明らかにした。(2)細胞骨格であるストレス繊維が、チャネルや接着斑と分子複合体を形成し機械刺激の伝達・収斂といった役割を担うこと、さらに、それ自体が機械刺激感知のセンサーであること、を見出した。(3)応用研究として新規機械刺激受容チャネルブロッカーの探索を行い、心臓の不整脈治療薬の候補を見出した。

  • Research Products

    (22 results)

All 2010 2009 2008 2007 2006 2005 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (8 results) Book (4 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Structural changes in the cytoplasmic domain of the mechanosensitive channel MscS during opening.2009

    • Author(s)
      Machiyama H, Tatsumi H, Sokabe M.
    • Journal Title

      Biophys J 97

      Pages: 1048-1057

    • Peer Reviewed
  • [Journal Article] Chlamydomonas PPR2 encodes a voltage-dependent calcium channel required for the flagellar waveform conversion.2009

    • Author(s)
      Fujiu K, Nakayama Y, Yanagisawa A, Sokabe M, Yoshimura K.
    • Journal Title

      Curr Biol 19

      Pages: 133-139

    • Peer Reviewed
  • [Journal Article] Mechanical Forces Facilitate Actin Polymerization at Focal Adhesions in a Zyxin-Dependent Manner.2008

    • Author(s)
      Hirata H, Tatsumi H, Sokabe M
    • Journal Title

      J Cell Sci 121

      Pages: 2795-2804

    • Peer Reviewed
  • [Journal Article] Stress fiber acts as a force-transmitting and-focusing structure to activate MS channels in endothelial cells.2008

    • Author(s)
      Hayakawa K, Tatsumi H, Sokabe M
    • Journal Title

      J Cell Sci 121

      Pages: 496-503

    • Peer Reviewed
  • [Journal Article] Interaction between the cytoplasmic and transmembrane domains of the mechanosensitive channel2008

    • Author(s)
      Nomura T, Sokabe M, Yoshimura K
    • Journal Title

      MscS. Biophys J 94

      Pages: 1638-45

    • Peer Reviewed
  • [Journal Article] Gating-associated conformational changes in the mechanosensitive channel2008

    • Author(s)
      Yoshimura K, Usukura J, Sokabe M
    • Journal Title

      MscL. PNAS 105

      Pages: 4033-4038

    • Peer Reviewed
  • [Journal Article] Lipid-protein interaction of the MscS mechanosensitive channel examined by scanning mutagenesis.2006

    • Author(s)
      Nomura T, Yoshimura K, Sokabe M
    • Journal Title

      Biophys J 91

      Pages: 2874-81

    • Peer Reviewed
  • [Presentation] Molecular Biophysics of mechanosensitive ion channels.2009

    • Author(s)
      Sokabe M
    • Organizer
      ymposium on Single molecules Physiology of ion channel and motor proteins, IUPS Congress 2009
    • Place of Presentation
      Kyoto, Japan(organizer)
    • Year and Date
      20090727-20090801
  • [Presentation] Role of cytoskeleton in mechanotransduction.2009

    • Author(s)
      Sokabe M
    • Organizer
      Gordon Research Conference: Cellular Osmoregulation & Mechanotransduction.
    • Place of Presentation
      Biddeford, ME USA(invited)
    • Year and Date
      20090705-20090710
  • [Presentation] Nanobiology of cell mechanotransduction.2009

    • Author(s)
      Sokabe M
    • Organizer
      First World Congress of International Academy of Nanomedicine (IANM)
    • Place of Presentation
      Sanya, Hainan, China(invited)
    • Year and Date
      20090611-20090614
  • [Presentation] Molecular dynamics simulations on the mechanosensitive ion channel.2009

    • Author(s)
      Sokabe M
    • Organizer
      Phuket, Thailand
    • Place of Presentation
      invited
    • Year and Date
      20090408-20090413
  • [Presentation] Biophysics of cell mechanosensor at work: structure function of an MS channel protein.2008

    • Author(s)
      Sokabe M
    • Organizer
      5th Structural Biology & Functional Genomics and 1st Biological Physics International Conference
    • Place of Presentation
      Singapore(invited)
    • Year and Date
      20081209-20081211
  • [Presentation] Molecular and cellular biophysics of mechanotransduction.2007

    • Author(s)
      Sokabe M
    • Organizer
      National Symposium on "Biophysics in Medicine and Biology". Ann Meeting of Ind Biophys Soc.
    • Place of Presentation
      Chandigar, India(invited)
    • Year and Date
      20071115-20071117
  • [Presentation] Overview. Molecular physiology of mechanosignaling in the cell.2007

    • Author(s)
      Sokabe M
    • Organizer
      Symposium on "Comparative aspects of mechanobiology" 7th ICCPB
    • Place of Presentation
      Salvador, Brazil(Organizer, invited)
    • Year and Date
      20070812-20070816
  • [Presentation] Plenary Lecture, Nanobiology of mechanotransduction in cells: basics and applications.2007

    • Author(s)
      Sokabe M
    • Organizer
      World Congr Bio Eng 2007
    • Place of Presentation
      Bangkok, Thailand(invited)
    • Year and Date
      20070709-20070711
  • [Book] Nanotechnology in mechanobiology: mechanical manipulation of cells and organelle while monitoring intra-cellular signaling.(Mechanosensing Biology)2010

    • Author(s)
      Tatsumi H, Hayakawa K, Sokabe M
    • Publisher
      Springer(in press)
  • [Book] Biophysical mechanisms of tesion-dependent formation of stress fibers from actin meshwork. In "Biomechanics at Micro-and Nanoscale Levels, Volume IV" ed.(Wada H. )2007

    • Author(s)
      Hirata H, Tatsumi H, Sokabe M.
    • Total Pages
      72-81
    • Publisher
      World Scientific Publishing
  • [Book] 機械刺激受容チャネル、In「生物物理学ハンドブック」2007

    • Author(s)
      曽我部正博, 石渡, 他編
    • Total Pages
      276-278
    • Publisher
      朝倉書店
  • [Book] Analysis of micro-and nano-mechanisms in the activation of cell mechanosensors. In“Biomechanics at Micro-and Nanoscale Levels: Introduction of The Project"2005

    • Author(s)
      Sokabe M
    • Total Pages
      29-34
    • Publisher
      Sanko Printing
  • [Remarks]

    • URL

      http://www.med.nagoya-u.ac.jp/physiol2

  • [Patent(Industrial Property Rights)] 細胞培養方法2010

    • Inventor(s)
      曽我部正博・古家喜四夫・田崎剛・鶴田仁志・福田始弘
    • Industrial Property Rights Holder
      名古屋大学・株式会社クラレ
    • Industrial Property Number
      特許・PCT/JP2009/051991
    • Filing Date
      2010-02-05
  • [Patent(Industrial Property Rights)] 細胞培養方法2009

    • Inventor(s)
      曽我部正博・古家喜四夫・田崎剛・鶴田仁志・福田始弘
    • Industrial Property Rights Holder
      名古屋大学・株式会社クラレ
    • Industrial Property Number
      特許・特願2008-026385
    • Filing Date
      2009-02-06

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Published: 2011-06-18   Modified: 2016-04-21  

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