Integrins: dynamic scaffolds for adhesion and signaling in platelets

Abstract

The major platelet integrin, alphaIIbbeta3, is required for platelet interactions with proteins in plasma and the extracellular matrices (ECMs) that are essential for platelet adhesion and aggregation during hemo stasis and arterial thrombosis. Lig and binding to alphaIIbbeta3 is controlled by inside-out signals that modulate receptor conformation and clustering. In turn, ligand binding triggers outside-in signals through alphaIIbbeta3 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 ofalphaIIbbeta3 and the related integrin, alphaVbeta3. These developments are discussed here, and current models of bidirectional alphaIIbbeta3 signaling are presented as frameworks for future investigations. An understanding that alphaIIbbeta3 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.