title: Normal Platelet Integrin Function in Mice Lacking Hydrogen Peroxide-Induced Clone-5 (Hic-5).
abstract: Integrin αIIbβ3 plays a central role in the adhesion and aggregation of platelets and thus is essential for hemostasis and thrombosis. Integrin activation requires the transmission of a signal from the small cytoplasmic tails of the α or β subunit to the large extracellular domains resulting in conformational changes of the extracellular domains to enable ligand binding. 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 tails. Previous studies suggested Hic-5 as a novel regulator of integrin αIIbβ3 activation and platelet aggregation in mice. To assess this in more detail, we generated Hic-5-null mice and analyzed activation and aggregation of their platelets in vitro and in vivo. Surprisingly, lack of Hic-5 had no detectable effect on platelet integrin activation and function in vitro and in vivo under all tested conditions. These results indicate that Hic-5 is dispensable for integrin αIIbβ3 activation and consequently for arterial thrombosis and hemostasis in mice.
authors.affiliation: Department of Experimental Biomedicine-Vascular Medicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Popp
authors.affiliation: Department of Experimental Biomedicine-Vascular Medicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Thielmann
authors.affiliation: Department of Experimental Biomedicine-Vascular Medicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.affiliation: Department of Experimental Biomedicine-Vascular Medicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Stegner
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism / Q000502:physiology; D006487:Hemostasis / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051419:Paxillin / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism / Q000503:physiopathology
chemical_list: D051419:Paxillin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D006861:Hydrogen Peroxide