The platelet cytoskeleton stabilizes the interaction between αIIbβ3 and its ligand and induces selective movements of ligand-occupied integrin

Abstract

Previously, we showed that a subpopulation of the major platelet integrin, αIIbβ3, co-sediments from detergent lysates with talin and other membrane skeleton proteins. Once αIIbβ3 has bound adhesive ligand in a platelet aggregate, the detergent-insoluble αIIbβ3 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, αIIbβ3 forms clusters when occupied by ligand and is selectively moved into the open canalicular system; αIIbβ3 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 αIIbβ3 to bind ligand is decreased, and the movement of ligand-occupied αIIbβ3 is prevented. Together with the previous findings, these results suggest that (i) membrane skeleton-associated αIIbβ3 is selectively induced to bind ligand in activated platelets, (ii) ligand-induced transmembrane signaling causes an altered association of membrane skeleton-associated αIIbβ3 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.