MEMBRANE-CYTOSKELETAL INTERACTIONS IN THE HUMAN PLATELET

人类血小板中的膜-细胞骨架相互作用

• 批准号: 3081772
• 负责人: KATHERINE AMBERSON HAJJAR
• 金额: $ 6.58万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-06-01 至 1989-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3081772
• 关键词: actins; affinity chromatography; ankyrins; antibody; band 3 protein; binding proteins; calmodulin; cell adhesion; cell membrane; cytoskeleton; electron microscopy; gel electrophoresis; hemostasis; human tissue; immunofluorescence technique; immunoprecipitation; laboratory rabbit; membrane activity; membrane fusion; membrane model; membrane proteins; microtubules; platelet activating factor; platelet aggregation; platelets; protein sequence; radionuclide double label; spectrin

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.

止血可以被看作是一系列复杂的膜介导的事件 最终导致血小板粘附、表面活化和聚集。 的 受体介导的刺激血小板的机制 表面导致血小板栓形成和凝血酶产生， 大部分未知。 然而，人们普遍认为， 细胞骨架在形状改变、脱粒和 止血过程中的表面粘附。 在红细胞中， 血影蛋白-锚蛋白-带3轴提供了细胞之间的详细联系 表面和膜下细胞骨架。 迄今为止，免疫反应形式 血影蛋白和锚蛋白在多种细胞中被发现， 组织，尽管它们的确切作用尚未完全确定。 目标 这项研究的目的是确定一个类似的spectrin-ankyrin-band 3 复杂的人血小板，并检查其作为一个潜在的调解人的作用， 血小板表面活化、聚集和粘附。 这些 调查将采用标准的生化分离技术， 以及二维肽图，免疫沉淀方法， 纯化蛋白的单特异性抗体，和荧光， 电镜 预计这些研究将提供 在分子水平上深入了解正常血小板 功能 此外，目前的工作可以扩大到包括一个 患者血小板中细胞骨架蛋白相互作用的分析 临床表现为止血和血栓形成障碍。

项目成果

Philadelphia chromosome-positive chronic myelogenous leukemia following apparent acute lymphoblastic leukemia.

明显急性淋巴细胞白血病后的费城染色体阳性慢性粒细胞白血病。

• DOI: 10.1177/000992288502400710
• 发表时间: 1985
• 期刊: Clinical pediatrics
• 影响因子: 1.6
• 作者: Hajjar,KA

Structural and functional analysis of spectrin from neonatal erythrocytes.

新生儿红细胞血影蛋白的结构和功能分析。

• DOI: 10.1016/0167-4838(85)90233-x
• 发表时间: 1985
• 期刊: Biochimica et biophysica acta
• 作者: Hajjar,KA

Glucocorticoids Induce Nondipping Blood Pressure by Activating the Thiazide-Sensitive Cotransporter.

• DOI: 10.1161/hypertensionaha.115.06977
• 发表时间: 2016-05
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Ivy JR;Oosthuyzen W;Peltz TS;Howarth AR;Hunter RW;Dhaun N;Al-Dujaili EA;Webb DJ;Dear JW;Flatman PW;Bailey MA
• 通讯作者: Bailey MA

Inhibition of the purinergic P2X7 receptor improves renal perfusion in angiotensin-II-infused rats.

• DOI: 10.1038/ki.2015.182
• 发表时间: 2015-11
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: Menzies RI;Howarth AR;Unwin RJ;Tam FW;Mullins JJ;Bailey MA
• 通讯作者: Bailey MA