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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL031491-04
Application #
3342657
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1983-12-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78713
Collier, N C; Wang, K (1992) Purification and properties of human platelet P235: talin. Methods Enzymol 215:99-109
Wang, K; Fanger, B O; Guyer, C A et al. (1989) Electrophoretic transfer of high-molecular-weight proteins for immunostaining. Methods Enzymol 172:687-96