Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
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.
|