Regulation of platelet function by the cytoskeleton.
The platelet cytoskeleton contains two actin filament-based components. One is the cytoplasmic actin filaments that fill the cytoplasm and mediate contractile events. The other is the membrane skeleton that coats the plasma membrane and regulates properties of the membrane such as its contours and stability and the lateral distribution of membrane glycoproteins. Recent work reviewed in this article indicates that the GP IIb-IIIa complex can associate with the membrane skeleton. Upon platelet activation, GP IIb-IIIa becomes competent to bind its adhesive ligand, fibrinogen. This induces a reorganization of the cytoskeleton such that the membrane skeletal proteins with which GP IIb-IIIa is associated become associated with underlying cytoplasmic filaments. As in focal contacts of cultured cells, this ligand-induced association of GP IIb-IIIa with cytoplasmic actin filaments regulates the ability of GP IIb-IIIa to bind adhesive ligand. Intracellular enzymes that are activated as a consequence of ligand binding to the GP IIb-IIIa complex include tyrosine kinase(s) and calpain, making these potential candidates for enzymes inducing the two-way signaling across the membrane. Additional candidates include phosphoinositide 3-kinase and protein kinase C, other enzymes that have been detected in focal contacts of aggregating platelets. Future studies identifying interactions between the GP IIb-IIIa complex and membrane skeletal proteins should help to further elucidate the significance of the GP IIb-IIIa in cytoskeleton interaction in regulating integrin-mediated transmembrane signaling in platelets.
Fox
J E
JE
Glastone Institute of Cardiovascular Disease, Department of Pathology, University of California, San Francisco 94140.
D000199:Actins / Q000502:physiology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D003599:Cytoskeleton / Q000502:physiology*; D005340:Fibrinogen / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology; D008024:Ligands; D010973:Platelet Adhesiveness / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D000199:Actins; D016023:Integrins; D008024:Ligands; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen