Identification of Hic‐5 as a novel regulatory factor for integrin αIIbβ3 activation and platelet aggregation in mice |
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| Authors: | X‐F LEI S ARITA T MINO N TAKEDA K KOU K ETO T YOSHIDA T MIYAZAKI S SHIODA A MIYAZAKI |
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| Institution: | 1. Department of Biochemistry, Showa University School of Medicine, Tokyo;2. Center for Animal Resources and Development, Kumamoto University, Kumamoto;3. Laboratory of Electronic Microscopy, Showa University, Tokyo;4. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto;5. Department of Clinical Toxicology, Showa University School of Pharmacy, Tokyo;6. Department of Anatomy, Showa University School of Medicine, Tokyo, Japan |
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| Abstract: | 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. |
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| Keywords: | focal adhesion protein Hic‐5 integrin platelet |
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