HUMAN ERYTHROCYTE MEMBRANE CYTOSKELETON ASSOCIATIONS

这项提议的目标是a)进一步详细地阐明 人红细胞膜蛋白质的分子间相互作用 骨骼；b)确定红细胞膜蛋白如何组装 发展；c)使用红细胞膜作为实验 用于了解膜结构和功能的易访问模型系统 在更复杂的细胞中。另一个新的感兴趣的领域是 恶性疟原虫侵袭人红细胞的机制 寄生虫。一般而言，这些研究将在以下情况下进行 已经纯化和鉴定的膜蛋白，以及 这些蛋白质之间的关联性将被定量评估。 具体项目有以下几个方面：1)研究 红细胞Anykrin和Anyrin的蛋白水解物片段 血影蛋白的定义寡聚态和条带的胞质结构域 3.2)一种新发现的钙调素结合蛋白的研究 红细胞膜骨架的组成及其测定的目的 它的蛋白质结合，以及钙对这些结合的调节 和钙调蛋白。3)将RBC评价作为模型系统进行研究 受体介导的内吞作用中的蛋白质关联，使用 最近从红细胞胞浆中纯化，转铁蛋白受体从 胎盘。4)迄今尚未鉴定的红细胞蛋白质的研究 包括提纯、最近邻分析和寻找异构体 在其他组织中。候选者将是Band 4.2，一种膜骨架形式的 带7和最近发现的钙调蛋白结合蛋白。5)组装 红白血病分化过程中红细胞膜骨架的变化 细胞。6)人红细胞侵袭机制的研究 恶性疟原虫裂殖子及裂殖子的纯化 与条带3相互作用的蛋白质。

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.