The platelet cytoskeleton stabilizes the interaction between alpha(IIb)beta(3) and its ligand and induces selective movements of ligand-occupied integrin

Previously, we showed that a subpopulation of the major platelet integrin, alpha(IIb)beta(3), co-sediments from detergent lysates with talin and other membrane skeleton proteins. Once alpha(IIb)beta(3) has bound adhesive ligand in a platelet aggregate, the detergent-insoluble alpha(IIb)beta(3) redistributes (along with the detergent-insoluble membrane skeleton proteins and a variety of signaling molecules) to a fraction that contains cytoplasmic actin filaments. Concomitantly, certain signaling molecules are activated, The present study shows that, in intact platelets, alpha(IIb)beta(3) forms clusters when occupied by ligand and is selectively moved into the open canalicular system; alpha(IIb)beta(3) that has not bound ligand remains diffusely distributed at the periphery of the cell. When cytoplasmic actin filaments are depolymerized by cytochalasins, the ability of alpha(IIb)beta(3) to bind ligand is decreased, and the movement of ligand-occupied alpha(IIb)beta(3) is prevented. Together with the previous findings, these results suggest that (i) membrane skeleton-associated alpha(IIb)beta(3) is selectively induced to bind ligand in activated platelets, (ii) ligand-induced transmembrane signaling causes an altered association of membrane skeleton-associated alpha(IIb)beta(3) with the cytoplasmic component of the cytoskeleton, (iii) ligand-induced cytoskeletal reorganizations stabilize the interaction between ligand and integrin, and (iv) ligand-occupancy triggers cytoskeletal reorganizations that result in selective movements of occupied ligand.