Molecular mechanism of mDia function in T cell activation
| Project/Area Number |
25860188
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General pharmacology
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| Research Institution | Kyoto University |
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Principal Investigator |
THUMKEO Dean 京都大学, 医学(系)研究科(研究院), 助教 (40372594)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | TCRシグナル / mDia / F-actin / T細胞 / 免疫抑制剤 / アクチン |
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| Outline of Final Research Achievements |
T cell receptor (TCR) signaling is triggered by binding of TCR to the cognate antigen presented by major histocompatibility (MHC) complex and mediated by microclusters of multiprotein complex. While the critical role of actin cytoskeleton in these processes has been suggested, the molecular mechanisms therein have yet to be characterized. In this work, we show that combined loss of mDia1 and mDia3, the formin family actin nucleators, impairs the TCR signaling and consequently blocks positive selection of thymocytes. Imaging experiments revealed impairment of TCR microcluster dynamics and large fluctuation of polymerized actin in mDia1/3-deficient thymocytes. Therefore, F-actin reorganization mediated by mDia1 and 3 is required for thymocyte TCR signaling and function.
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Report
(3 results)
Research Products
(12 results)
