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

基本信息

批准号：
3342658
负责人：
KUAN WANG
金额：
$ 7.49万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-12-01 至 1990-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3342658
关键词：
actins cell adhesion crosslink cytoskeleton electron microscopy high performance liquid chromatography homeostasis human tissue laboratory mouse monoclonal antibody muscle proteins myosins phosphorylation platelet aggregation platelets protein structure

项目摘要

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.

血小板是外周血中最小的成分，在血液中起着至关重要的作用止血作用。当血小板暴露于受损血管时，粘附在暴露的内皮下胶原蛋白上，改变形状并释放负责随后聚集的物质血小板，最终形成血栓。血小板收缩蛋白和细胞骨架已被提议提供运动力负责形态变化和活性颗粒内容物的分泌。运动机制的分子基础保持模糊。该提案代表了正在进行的研究计划的延伸，解决了两种主要收缩蛋白——细丝蛋白和 P235（本实验室最近鉴定的一种主要血小板蛋白）参与人类瞬时和动态的细胞质细胞骨架血小板。具体来说，我们建议（1）开展详细的细丝蛋白-肌动蛋白和 P235-肌动蛋白相互作用的生物物理特征评估细丝蛋白参与组织的假设含有肌动蛋白的微丝，P235 参与维持肌动蛋白的非丝状或丝状状态； (2) 研究完整血小板和分离血小板的组织和蛋白质关联通过抗体定位技术和化学方法确定细胞骨架交联技术。