2014 Fiscal Year Final Research Report
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 |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | LFA-1 / migration / Rap1 / Mst1 / Rab13 / cell polarization / leading edge |
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| 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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| Free Research Field |
免疫学
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