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Analysis of TCR signaling dependent mDia activation molecular mechanism

Research Project

Project/Area Number 15K18986
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionKyoto University

Principal Investigator

Thumkeo Dean  京都大学, 医学研究科, 特定准教授 (40372594)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsT細胞 / mDia / TCRシグナル / アクチン / 免疫抑制剤 / 低分子量G蛋白質
Outline of Final Research Achievements

T cell is essential for adaptive immunity. T cells is activated by TCR signaling that is indispensable for T cell development and function. I have previously reported that mDia facilitates TCR signaling through the regulation of actin polymerization by utilizing mDia 1/3 double deficient mice. In this study, I further unraveled the molecular mechanism of mDia activation in TCR signaling. We found that mDia is activated by the small G protein RhoA upon TCR stimulation. In addition, using T cells expressing EGFP-mDia3, I found that mDia is localized at the cell periphery in T cells upon TCR stimulation. Therefore, mDia is activated upon TCR stimulation through RhoA at the cell periphery and facilitate TCR signaling through its actin polymerization activity.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (10 results)

All 2017 2016 2015

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Constitutive activation of DIA1 (DIAPH1) via C-terminal truncation causes human sensorineural hearing loss2016

    • Author(s)
      Ueyama T, Ninoyu Y, Nishio S, Miyoshi T, Torii H, Nishimura K, Sugahara K, Sakata H, Thumkeo D, Sakaguchi H, Watanabe N, Usami S, Saito N, Kitajiri S
    • Journal Title

      EMBO Molecular Medicine

      Volume: 8 Pages: 1310-1324

    • NAID

      120005850206

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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)
      Katsura Y, Thumkeo D, Narumiya S
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎
    • Related Report
      2016 Annual Research Report
  • [Presentation] 目の発生におけるmDiaの機能解析2017

    • Author(s)
      Thumkeo D, Sakamoto S, Fu T, Narumiya S
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎
    • 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)
      Fu T, Sakamoto S, Thumkeo D, Narumiya S
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎
    • Related Report
      2016 Annual Research Report
  • [Presentation] グリオーマにおけるVasohibin-1の発現解析2017

    • Author(s)
      Yokogawa R, Thumkeo D, Arakawa Y
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎
    • 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)
      Dean Thumkeo, Satoko Sakamoto, Shuh Narumiya
    • Organizer
      第59回日本薬理学会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-10
    • Related Report
      2015 Research-status Report
  • [Presentation] Regulation of cortical F-actin meshwork architecture in Sertoli cell by mDia1/32016

    • Author(s)
      Dean Thumkeo, Satoko Sakamoto, Shuh Narumiya
    • Organizer
      生体運動合同班会議
    • Place of Presentation
      京都
    • Year and Date
      2016-01-08
    • Related Report
      2015 Research-status 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
      サンディエゴ、米国
    • Year and Date
      2015-12-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [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
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
  • [Presentation] Role of mDia in spermatogenesis2015

    • Author(s)
      Satoko Sakamoto, Dean Thumkeo, Masahito Ikawa, Yoshitaka Fujiwara, Hiroshi Ohta, Sadanori Watanabe, Shuh Narumiya
    • Organizer
      第67回日本細胞生物学会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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