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Physiological roles and action mechanisms of mDia-induced actin cytoskeleton in the body

Research Project

Project/Area Number 26221302
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionKyoto University

Principal Investigator

Narumiya Shuh  京都大学, 医学研究科, 教授 (70144350)

Co-Investigator(Kenkyū-buntansha) 石崎 敏理  大分大学, 医学部, 教授 (70293876)
Project Period (FY) 2014-05-30 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥172,120,000 (Direct Cost: ¥132,400,000、Indirect Cost: ¥39,720,000)
Fiscal Year 2016: ¥49,400,000 (Direct Cost: ¥38,000,000、Indirect Cost: ¥11,400,000)
Fiscal Year 2015: ¥49,400,000 (Direct Cost: ¥38,000,000、Indirect Cost: ¥11,400,000)
Fiscal Year 2014: ¥73,320,000 (Direct Cost: ¥56,400,000、Indirect Cost: ¥16,920,000)
Keywordsアクチン / Rho / mDia / シナプス / T細胞 / 精子形成 / 皮膚腫瘍 / 神経可塑性 / T 細胞 / 皮膚がん化 / TCRシグナリング / 腫瘍形成 / アクチン細胞骨格 / 細胞悪性化
Outline of Final Research Achievements

While the actin cytoskeleton plays an important role in cell morphogenesis, adhesion,migration and division,its role in various body functions remains largely obscure.In this study we examined this issue by generating KO mice deficient in mDia, an actin polymerizing factor, and analyzing their phenotypes in the brain, the immune system, the reproductive system and tumorigenesis. In the brain, mDia-induced actin cytoskeleton is critically involved in synaptic remodeling that is required for social isolation-induced elevated anxiety. mDia-induced actin cytoskeleton is also involved in T cell activation by regulating dynamics of antigen-bound T cell receptors, morphogenesis of sperm by regulating interaction between germ cells and Sertoli cells in the testis and malignant cell transformation and tumorigenesis by interaction with Ras in chemical carcinogenesis model in the skin.

Assessment Rating
Verification Result (Rating)

A-

Result (Rating)

A-: Progress in the research is steadily towards the initial goal. However, further efforts are necessary as a part of the research progress is delayed.

Report

(8 results)
  • 2017 Research Progress Assessment (Verification Result) ( PDF )
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report   Abstract(Research Progress Assessment) ( PDF )   Research Progress Assessment (Result) ( PDF )
  • 2014 Abstract ( PDF )   Annual Research Report

Research Products

(26 results)

All 2017 2016 2015 2014

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (23 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] mDia and ROCK mediate actin-dependent presynaptic remodeling regulating synaptic efficacy and anxiety.2016

    • Author(s)
      Deguchi Y, Harada M, Shinohara R, Lazarus M, Cherasse Y, Urade Y, Yamada D, Sekiguchi M, Watanabe D, Furuyashiki T, Narumiya S.
    • Journal Title

      Cell Rep.

      Volume: 17 Pages: 24052417-24052417

    • DOI

      10.1016/j.celrep.2016.10.088

    • NAID

      120005868496

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a2016

    • Author(s)
      Yamaoka M, Ando T, Terabayashi T, Okamoto M, Takei M, Nishioka T, Kaibuchi K, Matsunaga K, Ishizaki R, Izumi T, Niki I, Ishizaki T, Kimura T
    • Journal Title

      J. Cell Sci.

      Volume: 129 Pages: 637-649

    • DOI

      10.1242/jcs.180141

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 免疫シナプスにおけるmDia1/3依存的なF-actinの機能解析2017

    • Author(s)
      桂善親、タムケオ ディーン、成宮周
    • Organizer
      第90回 日本薬理学会年会
    • Place of Presentation
      長崎:長崎パブリックホール
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 目の発生におけるmDiaの機能解析2017

    • Author(s)
      タムケオ ディーン、坂本智子、符毅欣、成宮周
    • Organizer
      第90回 日本薬理学会年会
    • Place of Presentation
      長崎:長崎パブリックホール
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 精子形成におけるmDia1/3の機能解析2017

    • Author(s)
      符毅欣、坂本智子、タムケオ ディーン、成宮周
    • Organizer
      第90回 日本薬理学会年会
    • Place of Presentation
      長崎:長崎パブリックホール
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] Role of Rho-mDia1 Signaling in the Pressure Overload-Induced Cardiac Hypertrophic Response2017

    • Author(s)
      Ichitaro Abe, Y Teshima, Y Yonehara, H Kaku, S Kira,T Oniki, Y Ikebe, H Kondo, S Saito, T Terabayashi, T Ishizaki, Naohiko Takahashi
    • Organizer
      第81回日本循環器学会学術集会
    • Place of Presentation
      金沢:石川県立音楽堂
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 心肥大応答におけるmDiaの役割2016

    • Author(s)
      安部一太郎、手嶋泰之、寺林健、石崎敏理、髙橋尚彦
    • Organizer
      第26回日本病態生理学会
    • Place of Presentation
      金沢: 金沢医科大学
    • Year and Date
      2016-08-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Indispensable role of mDia1/3 in sperm morphogenesis through the remodeling of Sertoli cell meshwork F-actin2016

    • Author(s)
      タムケオ ディーン、坂本智子、成宮周
    • Organizer
      第89回日本薬理学会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-03-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Regulation of cortical F-actin meshwork architecture in Sertoli cell by mDia1/32016

    • Author(s)
      タムケオ ディーン、坂本智子、成宮周
    • Organizer
      生体運動合同班会議
    • Place of Presentation
      京都市
    • Year and Date
      2016-01-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Roles of mDia1/3 in neuroepithelium integrity and neuroblast migration2015

    • Author(s)
      Dean Thumkeo, Ryota Shinohara, Shuh Narumiya
    • Organizer
      The 56th Annual Meeting of the American Society for Cell Biology
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-12-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵B細胞におけるエンドサイトーシスの時間的・空間的制御機構の解析2015

    • Author(s)
      山岡真美、寺林健、松永耕一、泉哲郎、仁木一郎、石崎敏理、木村俊秀
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] マウス社会隔離ストレスによる不安亢進とシナプス前終末可塑性におけるRho制御アクチン重合因子mDiaの役割2015

    • Author(s)
      出口 雄一
    • Organizer
      生理学研究所研究会『情動研究会』「感覚刺激・薬物による快・不快情動生成機構とその破綻」
    • Place of Presentation
      岡崎市
    • Year and Date
      2015-10-07
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] マウス社会隔離ストレスによる不安亢進とシナプス前終末可塑性とにおけるRho制御アクチン重合因子mDiaの役割2015

    • Author(s)
      出口 雄一
    • Organizer
      第45回日本神経精神薬理学会、第37回日本生物学的精神医学会、合同年会
    • Place of Presentation
      東京都
    • Year and Date
      2015-09-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] mDia1/3-mediated cortical F-actin assembly is required for T cell receptor signaling2015

    • Author(s)
      Dean Thumkeo, Kiyoshi Tohyama, Pakorn Kanchanawong, Shuh Narumiya
    • Organizer
      第67回日本細胞生物学会
    • Place of Presentation
      東京都
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 精子形成におけるRho標的タンパク質・フォルミンファミリーアクチン核化因子mDiaの役割解明2015

    • Author(s)
      坂本智子、タムケオ ディーン、伊川正人、藤原祥高、大田浩、渡邉定則、成宮周
    • Organizer
      第67回日本細胞生物学会
    • Place of Presentation
      東京都
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 膵B細胞におけるエンドサイトーシスの時間的・空間的制御機構の解析2015

    • Author(s)
      山岡真美、安藤朋海、寺林健、松永耕一、泉哲郎、仁木一郎、石崎敏理、木村俊秀
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      山口市
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Formin family actin nucleators, mDia1 and mDia3, mediate TCR microcluster dynamics and signaling critical for positive selection of thymocytes.2015

    • Author(s)
      Thumkeo, D., Nomachi, A., Tohyama, K., and Narumiya, S.
    • Organizer
      The 88th Annual Meeting of the Japanese Pharmacological Society.
    • Place of Presentation
      Nagoya, Japan
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] T cell cortical F-actin is mediated by mDia and critical for TCR signaling.2015

    • Author(s)
      Tohyama, K., Thumkeo, D., and Narumiya, S.
    • Organizer
      The 88th Annual Meeting of the Japanese Pharmacological Society.
    • Place of Presentation
      Nagoya, Japan
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] mDia1 and mDia3, formin family actin nucleators and Rho effectors, mediate TCR microcluster dynamics and signaling and are critical for positive selection of thymocytes.2014

    • Author(s)
      Narumiya, S., Thumkeo, D., Beemiller, O. and Krummel, M.F.
    • Organizer
      The 2014 Cold Spring Harbor Asia Conference on “GTPases: Mechanisms, interactions and applications”
    • Place of Presentation
      Suzhou, China
    • Year and Date
      2014-09-22 – 2014-09-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] A role for mDia, a Rho-regulated actin nucleator, in chronic stress-induced behavioral changes and synaptic plasticity.2014

    • Author(s)
      Deguchi, Y., Harada, M., Shinohara, R., Watanave, D., Furuyashiki, T., and Narumiya, S.
    • Organizer
      The 2014 Cold Spring Harbor Asia Conference on “GTPases: Mechanisms, interactions and applications”
    • Place of Presentation
      Suzhou, China
    • Year and Date
      2014-09-22 – 2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] A role for mDia, a Rho-regulated actin nucleator, in chronic stress-induced behavioral changes and synaptic plasticity.2014

    • Author(s)
      Deguchi, Y., Harada, M., Shinohara, R., Lazarus, M., Cherasse, Y., Urade, Y., Watanabe, D., Furuyashiki, T., and Narumiya, S.
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] A role for mDia, a Rho-regulated actin nucleator, in regulating morphology of presynaptic terminals and increased anxiety-like behavior induced by social isolation stress in mice.2014

    • Author(s)
      Deguchi, Y., Harada, M., Shinohara, R., Lazarus, M., Cherasse, Y., Urade, Y., Watanabe, D., Furuyashiki T., and Narumiya, S.
    • Organizer
      The 88th Annual Meeting of the Japanese Pharmacological Society
    • Place of Presentation
      Nagoya, Japan
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Indispensable role of formin family actin nucleator, mDia1 and mDia3, in TCR microcluster dynamics and signaling critical for positive selection of thymocytes.2014

    • Author(s)
      Thumkeo, D., Beemiller, P., Nomachi, A., Krummel, M.F. and Narumiya, S.
    • Organizer
      The 37th Naito Conference “Bioimaging-a paradigm shift for the life science”.
    • Place of Presentation
      Niseko, Hokkaido, Japan
    • Year and Date
      2014-07-15 – 2014-07-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of mDia in Spermatogenesis.2014

    • Author(s)
      Sakamoto, S., Thumkeo, D., and Narumiya, S.
    • Organizer
      he 66th Annual Meeting of the Japanese Society for Cell Biology.
    • Place of Presentation
      Nara, Japan
    • Year and Date
      2014-06-11 – 2014-06-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] The formin protein mDia is indispensible for TCR signaling dependent T cell development through actin nucleation activity.2014

    • Author(s)
      Thumkeo, D., Beemiller, P., Nomachi, A., Krummel, M.F. and Narumiya, S.
    • Organizer
      The 66th Annual Meeting of the Japanese Society for Cell Biology
    • Place of Presentation
      Nara, Japan
    • Year and Date
      2014-06-11 – 2014-06-13
    • Related Report
      2014 Annual Research Report
  • [Book] Molecular structures, cellular functions, and physiological roles of Rho effectors in Ras Superfamily Small G Proteins: Biology and Mechanisms (ed. Alfred Wittinghofer)2014

    • Author(s)
      Ishizaki T and Narumiya S
    • Total Pages
      742
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-06-05   Modified: 2018-04-24  

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