Hemostasis can be viewed as a complex series of membrane-mediated events culminating in platelet adhesion, surface activation, and aggregation. The mechanisms through which a receptor-mediated stimulus at the platelet surface leads to platelet plug formation and generation of thrombin are largely unknown. It is generally recognized, however, that the platelet cytoskeleton plays a critical role in shape change, degranulation, and surface adhesion during the hemostatic process. In the erythrocyte, the spectrin-ankyrin-band 3 axis provides a detailed linkage between the cell surface and the submembranous cytoskeleton. To date, immunoreactive forms of both spectrin and ankyrin have been found in a variety of cells and tissues, although their precise roles are not yet fully defined.
The aims of this study will be to identify an analog of the spectrin-ankyrin-band 3 complex in human platelets, and to examine its role as a potential mediator of platelet surface activation, aggregation and adhesion. These investigations will employ standard biochemial separation techniques, as well as two-dimensional peptide mapping, immunoprecipitation methods using monospecific antibodies to purified proteins, anad fluorescence and electron microscopy. It is anticipated that these studies will provide insight, on a molecular level, into the mechanisms of normal platelet function. In addition, the present work could be extended to include an analysis of cytoskeletal protein interactions in platelets from patients with clinical disorders of hemostasis and thrombosis.
