MEMBRANE DYNAMICS IN NORMAL AND ABNORMAL ERYTHROID CELLS

成熟和分化的红系细胞的质膜都是 对细胞内和细胞内变化做出反应的动态结构 细胞外环境。该提案使用时间分辨激光和 视频显微技术，包括荧光光漂白 恢复、偏振荧光耗尽、定量荧光 成像和纳米视频显微镜，以研究分子机制 调节人红细胞膜表面受体的迁移和分布 血细胞、红细胞、网织红细胞和红白血病细胞 膜和包括尿液在内的红系分化模型 红白血病细胞、小鼠红系母细胞和网织红细胞。我们 研究特定结合作用的作用，空间位阻 控制中的相互作用、络合物形成和聚集体形成 红细胞主要跨膜的迁移率和分布 蛋白质，带3和血糖蛋白A。我们研究了 从循环中去除衰老的红细胞，重点放在 带3聚集、表面免疫球蛋白沉积和 磷脂酰丝氨酸从叶内到叶外的移位 红细胞膜。我们研究了质膜机制， 控制转铁蛋白受体的迁移率和分布 红白血病细胞中纤维连接蛋白受体与红系发育 细胞培养中受体的配体占有率对这些细胞的影响 过程以及红系细胞之间的相互作用 受体动力学和表达的分化和调节。这个 这项研究的长期目标是了解分子细节， 调节跨膜流动性和分布的力量 红细胞膜中蛋白质和脂质之间的关系 这些调节机制的紊乱及其病理生理学 膜状态异常与疾病的关系 这些控制机制的变化和细胞生理学 红系细胞发育。

Plasma membranes of both mature and differentiating erythroid cells are dynamic structures that respond to changes in the intracellular and extracellular environment. This proposal uses time resolved laser and video microscopy techniques, including fluorescence photobleaching recovery, polarized fluorescence depletion, quantitative fluorescence imaging, and nanovid microscopy, to study the molecular mechanisms that regulate cell surface receptor mobility and distribution in human red blood cell, erythroblast, reticulocyte, and erythroleukemia cell membranes and in models of erythroid differentiation including urine erythroleukemia cells and murine erythroblasts and reticulocytes. We investigate the roles of specific binding interactions, steric hindrance interactions, complex formation, and aggregate formation in controlling the mobility and distribution of the major red cell transmembrane proteins, band 3 and glycophorin A. We study the molecular basis for the removal of senescent red cells from the circulation, focusing on the roles of band 3 aggregation, surface immunoglobulin deposition, and translocation of phosphatidylserine from the inner to the outer leaflet of the red cell membrane. We examine the plasma membrane mechanisms that control the mobility and distribution of transferrin receptors and fibronectin receptors in erythroleukemia cells and developing erythroid cells in culture, the influence of receptor occupancy by ligand on these processes, and the mutual interactions between erythroid cell differentiation and regulation of receptor dynamics and expression. The long term goal of this research is to understand, in molecular detail, the forces that regulate the mobility and distribution of transmembrane proteins and lipids in erythroid cell membranes, the relationship between derangements in these regulatory mechanisms and the pathophysiology of disease in abnormal membrane states, and the relationship between alterations in these control mechanisms and the cellular physiology of erythroid cell development.