Rab13 is a downstream effector of Mst1 to mediate LFA-1 activation critical for lymphocyte trafficking.
Project/Area Number |
24590588
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Immunology
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Research Institution | Kitasato University |
Principal Investigator |
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Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | LFA-1 / migration / Rap1 / Mst1 / Rab13 / cell polarization / leading edge / 接着カスケード / インテグリン / 遊走 / 細胞極性 / ケモカイン / 動態 / シグナル伝達 / 免疫動態 |
Outline of Final Research Achievements |
In this study, we report an essential link between Rab13 and Mst1 in lymphocyte adhesion and migration. Mst1 promoted the phosphorylation of DENND1C to activate Rab13 with chemokine. Active Rab13 associated with Mst1, and facilitated to deliver LFA-1 to the leading edge of lymphocytes by recruitment of myosin Va along actin cables, which extended through the localization of VASP to the cell periphery via MST1-dependent phosphorylation at Ser-157. The inhibition of Rab13 function reduced adhesion and migration on ICAM-1, and LFA-1 ring formation of T cells at contact zone with antigen-presenting cells. Rab13-deficient mice had hypoplastic lymphoid tissues due to the defective trafficking capability of lymphocytes. These results indicate that Rab13 acts with Mst1 to regulate the spatial distribution of LFA-1, and the motility and interaction dynamics of lymphocytes.
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Report
(4 results)
Research Products
(10 results)