THE ROLE OF CYTOSKELETAL PROTEINS IN PLATELET PHYSIOLOGY

细胞骨架蛋白在血小板生理学中的作用

• 批准号: 3342655
• 负责人: KUAN WANG
• 金额: $ 7.34万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3342655
• 关键词: cell adhesion; crosslink; cytoskeleton; electron microscopy; high performance liquid chromatography; homeostasis; human tissue; monoclonal antibody; muscle proteins; phosphorylation; platelet aggregation; platelets

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.

血小板是外周血液中最小的成分，在人体内起着至关重要的作用。 止血作用。当血小板暴露在受损的血管中时，它们 黏附裸露的内皮下胶原蛋白，变形释放 对随后的聚集负责的物质 血小板，最终导致血栓形成。血小板膜 收缩蛋白和细胞骨架被认为提供了 运动力既是形态变化的原因，也是活动的原因 分泌颗粒内容物。运动机制的分子基础 仍然令人费解。 这项提案代表着一项正在进行的研究计划的延伸， 解决了两种主要的收缩蛋白，丝氨酸和 P235(本实验室最近鉴定的一种主要的血小板蛋白) 参与人体瞬时和动态的胞浆细胞骨架 血小板。具体地说，我们建议(1)开展详细的 丝氨酸-肌动蛋白和P235-肌动蛋白相互作用的生物物理特征 来评估细丝蛋白参与组织的假说 含有肌动蛋白的微丝，而P235参与维持 肌动蛋白的非丝状或前丝状状态；(2)研究 完整和分离的血小板中的组织和蛋白质结合 用抗体定位技术和化学方法研究细胞骨架 交联剂技术。