HUMAN ERYTHROCYTE MEMBRANE CYTOSKELETON ASSOCIATIONS

人类红细胞膜细胞骨架协会

• 批准号: 3229056
• 负责人: G Vann Bennett
• 金额: $ 19.95万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3229056
• 关键词: Plasmodium falciparum; ankyrins; band 3 protein; binding proteins; calcium; calmodulin; clathrin; cow; crosslink; cytoskeleton; electron microscopy; erythrocyte membrane; erythroleukemia; gel electrophoresis; human tissue; laboratory rabbit; malaria; membrane proteins; phosphorylation; protein structure; radioimmunoassay; radiotracer; spectrin; transferrin; transferrin receptor; virulence

The goals of this proposal are to a) elucidate in further detail the intermolecular associations of proteins of the human erythrocyte membrane skeleton; b) determine how membrane proteins assemble during erythroid development; c) use the erythrocyte membrane as an experimentally accessible model system for understanding membrane structure and function in more complex cells. An additional, new area of interest is the mechanism of invasion of human erythrocytes by P. falciparum malarial parasites. As a general approach, these studies will be performed with membrane proteins that have been purified and characterized, and associations between these proteins will be evaluated quantitatively. Specific projects are in the following areas: 1) Studies of binding of erythrocyte anykrin and proteolytic fragments of ankyrin in solution to defined oligomeric states of spectrin and the cytoplasmic domain of band 3. 2) Studies of a newly discovered calmodulin-binding protein that is a component of the erythrocyte membrane skeleton with goals of determining its protein associations, and regulation of these associations by calcium and calmodulin. 3) Evaluation of the RBC as a model system to study protein associations in receptor-mediated endocytosis, using clathrin that has recently been purified from RBC cytosol, and transferrin receptor from placenta. 4) Studies of heretofore uncharacterized erythrocyte proteins including purification, nearest neighbor analysis and search for isoforms in other tissues. Candidates will be band 4.2, a membrane skeletal form of band 7 and a recently discovered calmodulin-binding protein. 5) Assembly of an erythroid membrane skeleton during differentiation of erythroleukemia cells. 6) Studies of the mechanisms of invasion of human erythrocytes by merozoites of P. falciparum, with emphasis on purification of merozoite proteins that interact with band 3.

该提案的目标是a）进一步详细阐明 人红细胞膜蛋白质的分子间关联 骨骼; b）确定膜蛋白在红细胞过程中如何组装 发展; c）将红细胞膜用作实验 可访问的模型系统，用于了解膜结构和功能 在更复杂的细胞中。 另一个新的感兴趣领域是 恶性疟原虫疟疾侵袭人红细胞的机制 寄生虫。 作为一般方法，这些研究将与 已被纯化和表征的膜蛋白，并且 这些蛋白质之间的关联将进行定量评估。 特定项目在以下领域：1）结合的研究 红细胞Anykrin和Ankyrin的蛋白水解片段 定义的光谱的寡聚状态和带的细胞质结构域 3。2）对新发现的钙调蛋白结合蛋白的研究，这是一种 红细胞膜骨骼的组成部分，确定目标 其蛋白质关联，并通过钙调节这些关联 和钙调蛋白。 3）评估RBC作为研究模型系统 使用网格蛋白 最近已从RBC细胞质纯化，并从 胎盘。 4）迄今未表征的红细胞蛋白的研究 包括纯化，最近的邻居分析和搜索同工型 在其他组织中。 候选人将是Band 4.2，一种膜骨骼形式 带7和最近发现的钙调蛋白结合蛋白。 5）组装 红细胞血症分化期间的红细胞膜骨骼 细胞。 6）研究人类侵袭人红细胞的机制 恶性疟原虫的梅罗寄生虫，重点是纯化梅罗唑群体 与频带3相互作用的蛋白质。