THE ROLE OF CYTOSKELETAL PROTEINS IN PLATELET PHYSIOLOGY

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Platelets, the smallest components of peripheral blood, play an essential role in hemostasis. When platelets are exposed to damaged vessels, they adhere to the exposed subendothelial collagen, change shape and release substances which are responsible for the subsequent aggregation of platelets, ultimately leading to the formation of a thrombus. The platelet contractile proteins and cytoskeleton have been proposed as providing the motile force responsible for both the morphological changes and the active secretion of granule contents. The molecular basis of the motile mechanism remain obscrue. This proposal, representing an extension of an on-going research program, addresses the question of how two major contractile proteins, filamin and P235 (a major platelet protein recently characterized in this laboratory) are involved in the transient and dynamic cytoplasmic cytoskeleton of human platelets. Specifically, we propose (1) to carry out a detailed biophysical characterization of filamin-actin and P235-actin interactions to evaluate the hypothesis that filamin is involved in the organization of actin-containing microfilaments, and that P235 is involved in maintaining the nonfilamentous or profilamentous state of actin; (2) to study the organization and protein association in intact platelet and in the isolated cytoskeleton by antibody localization techniques and by chemical crosslinking techniques.