2013 Fiscal Year Final Research Report
Identification of Hic-5 as a novel regulatory factor for integrin aIIbb3 activation and platelet aggregation in mice.
| Project/Area Number |
23791090
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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 |
Hematology
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| Research Institution | Showa University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Keywords | 血栓・止血学 |
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| Research Abstract |
Hic-5, a member of the paxillin family, serves as a focal adhesion adaptor protein associated with aIIbb3. Hic-5 function in aIIbb3 activation and subsequent platelet aggregation remains unknown. To address this question, platelets from Hic-5-/- mice were analyzed. Hic-5-/- mice displayed a significant hemostatic defect and resistance to thromboembolism, which were explained in part by weaker thrombin-induced aggregation in Hic-5-/- platelets. Mechanistically, Hic-5-/- platelets showed limited activation of aIIbb3 upon thrombin treatment. Morphological alteration in Hic-5-/- platelets after thrombin stimulation on fibrinogen plates was also limited. As a direct consequence, the quantity of actin co-immunoprecipitating with the activated aIIbb3 was smaller in Hic-5-/- platelets than in wild-type platelets.We identified Hic-5 as a novel and specific regulatory factor for thrombin-induced aIIbb3 activation and subsequent platelet aggregation in mice.
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