Platelet membrane αllbβ3 (glycoprotein ilb-iiia)

The capacity of platelets to adhere to other platelets and to specific elements within the extracellular matrix is a control point for the maintenance of normal hemostasis. Within the vasculature, platelets circulate without apparent affinity for other platelets; however, in areas of vessel or tissue trauma, platelets will rapidly attach, spread, and aggregate to prevent excessive loss of blood. Failure of this remarkably fine tuned system is associated with a host of serious side effects including severe bleeding and thrombosis. The membrane glycoprotein αIIbβ3 (GP IIb-IIIa) complex plays a central role in the aggregation response by mediating the interaction of platelets with fibrinogen and other adhesive proteins in plasma including fibronectin and the von Willebrand factor. The original observations indicating the essential role αIIbβ3 plays in platelet aggregation were derived from studies of patients with the inherited bleeding disorder, Glanzmann’s thrombasthenia. Platelets from affected individuals possess marked deficiencies in αIIbβ3 content and/or function and are characterized by a lack of adhesive protein binding and, subsequently, the absence of platelet aggregation. In addition to its role in hemostatic processes, studies of αIIbβ3 structure-function have had broad implications for cell adhesion in general with the realization of the existence of the integrin superfamily of functionally and structurally related adhesion receptors. αIIbβ3 (GPIIb-IIIa in the platelet nomenclature) was a charter member of this adhesion receptor family, has figured prominently in its establishment, and has provided fundamental insights into the molecular mechanisms underlying cell adhesion. Indeed, αIIbβ3 was among the first of the integrins to be identified, purified, cloned, and sequenced, and the first to be expressed in a completely recombinant form.