Integrins: Dynamic scaffolds for adhesion and signaling in platelets

Abstract

The major platelet integrin, αIIbβ3, is required for platelet interactions with proteins in plasma and the extracellular matrices (ECMs) that are essential for platelet adhesion and aggregation during hemostasis and arterial thrombosis. Ligand binding to αIIbβ3 is controlled by inside-out signals that modulate receptor conformation and clustering. In turn, ligand binding triggers outside-in signals through αIIbβ3 that, when disrupted, can cause a bleeding diathesis. In the past 5 years there has been an explosion of knowledge about the structure and function of αIIbβ3 and the related integrin, αVβ3. These developments are discussed here, and current models of bidirectional αIIbβ3 signaling are presented as frameworks for future investigations. An understanding that αIIbβ3 functions as a dynamic molecular scaffold for extracellular and intracellular proteins has translated into diagnostic and therapeutic insights relevant to hematology and cardiovascular medicine, and further advances can be anticipated. © 2004 by The American Society of Hematology.