• focal adhesion protein;
  • Hic-5;
  • integrin;
  • platelet

Summary.  Background:  Integrin αIIbβ3 plays key roles in platelet aggregation and subsequent thrombus formation. Hydrogen peroxide-inducible clone-5 (Hic-5), a member of the paxillin family, serves as a focal adhesion adaptor protein associated with αIIbβ3 at its cytoplasmic strand.

Objectives:  Hic-5 function in αIIbβ3 activation and subsequent platelet aggregation remains unknown. To address this question, platelets from Hic-5−/− mice were analyzed.

Methods and Results:  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 αIIbβ3 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 αIIbβ3 was smaller in Hic-5−/− platelets than in wild-type platelets.

Conclusion:  We identified Hic-5 as a novel and specific regulatory factor for thrombin-induced αIIbβ3 activation and subsequent platelet aggregation in mice.