The structure and function of platelet integrins

Integrins are a ubiquitous family of non-covalently associated alpha/beta transmembrane heterodimers linking extracellular ligands to intracellular signaling pathways [1] [Cell, 2002; 110: 673]. Platelets contain five integrins, three beta 1 integrins that mediate platelet adhesion to the matrix proteins collagen, fibronectin and laminin, and the beta 3 integrins alpha v beta 3 and alpha IIb beta 3 [2] [J Clin Invest, 2005; 115: 3363]. While there are only several hundred alpha v beta 3 molecules per platelet, alpha v beta 3 mediates platelet adhesion to osteopontin and vitronectin in vitro [3] [J Biol Chem, 1997; 272: 8137]; whether this occurs in vivo remains unknown. By contrast, the 80 000 alpha IIb beta 3 molecules on agonist-stimulated platelets bind fibrinogen, von Willebrand factor, and fibronectin, mediating platelet aggregation when the bound proteins crosslink adjacent platelets [2] [J Clin Invest, 2005; 115: 3363]. Although platelet integrins are poised to shift from resting to active conformations, tight regulation of their activity is essential to prevent the formation of intravascular thrombi. This review focuses on the structure and function of the intensively studied beta 3 integrins, in particular alpha IIb beta 3, but reference will be made to other integrins where relevant.