Both authors contributed equally to this study.
Identification of Hic-5 as a novel regulatory factor for integrin αIIbβ3 activation and platelet aggregation in mice
Version of Record online: 4 SEP 2012
© 2012 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 10, Issue 9, pages 1867–1874, September 2012
How to Cite
KIM-KANEYAMA, J.-R., MIYAUCHI, A., LEI, X.-F., ARITA, S., MINO, T., TAKEDA, N., KOU, K., ETO, K., YOSHIDA, T., MIYAZAKI, T., SHIODA, S. and MIYAZAKI, A. (2012), Identification of Hic-5 as a novel regulatory factor for integrin αIIbβ3 activation and platelet aggregation in mice. Journal of Thrombosis and Haemostasis, 10: 1867–1874. doi: 10.1111/j.1538-7836.2012.04856.x
- Issue online: 4 SEP 2012
- Version of Record online: 4 SEP 2012
- Accepted manuscript online: 20 JUL 2012 01:05AM EST
- Received 13 October 2011, accepted 1 July 2012
- focal adhesion protein;
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.