MEMBRANE DYNAMICS IN NORMAL AND ABNORMAL ERYTHROID CELLS

成熟和分化中的红系细胞的质膜都是 动态结构，响应细胞内的变化， 细胞外环境 该建议使用时间分辨激光器， 视频显微镜技术，包括荧光光漂白 回收率，偏振荧光衰减，定量荧光 成像和nanovid显微镜，以研究分子机制， 调节人红细胞表面受体的迁移和分布 血细胞、成红细胞、网织红细胞和红白血病细胞 膜和红细胞分化模型，包括尿 红白血病细胞和鼠成红细胞和网织红细胞。 我们 研究特异性结合相互作用、空间位阻 相互作用、复合物形成和聚集体形成， 主要红细胞跨膜的流动性和分布 带3和血型糖蛋白A。 我们研究了 从血液循环中清除衰老的红细胞， 带3聚集、表面免疫球蛋白沉积和 磷脂酰丝氨酸从内叶转移到外叶 红细胞膜。 我们研究了质膜机制， 控制转铁蛋白受体的移动性和分布， 红白血病细胞和发育中红系细胞的纤连蛋白受体 培养的细胞，配体对这些细胞的受体占有率的影响， 过程，以及红系细胞之间的相互作用 分化和调节受体动力学和表达。 的 这项研究的长期目标是，从分子的细节上， 调节跨膜细胞迁移和分布的力 红系细胞膜中的蛋白质和脂质， 这些调节机制的紊乱和 膜状态异常的疾病，以及 这些控制机制和细胞生理学的改变， 红细胞发育

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.