RPE cell biology, aging, and disease

RPE 细胞生物学、衰老和疾病

• 批准号: 9765536
• 负责人: DAVID S WILLIAMS
• 金额: $ 30万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765536
• 关键词: Actins; Affect; Aging; Apical; Biology of Aging; Cathepsins; Cells; Cellular biology; Complement; Data; Defect; Dictyostelium; Disease; Dynein ATPase; Elements; Endosomes; Event; Frequencies; Gene Mutation; Genetic; Goals; Health; Homeostasis; Image Analysis; Immunofluorescence Immunologic; Ingestion; Kinesin; Knowledge; Link; Lysosomes; MYO7A gene; Macular degeneration; Membrane; Microtubules; Molecular; Motor; Movement; Myosin ATPase; Nature; Organelles; Pathogenesis; Pathology; Phagocytosis; Phagosomes; Phenotype; Photoreceptors; Process; Proteins; Research; Retinal; Retinal Degeneration; Retinal Diseases; Role; Running; Series; Site; Speed; Stargardt' s disease; Structure of retinal pigment epithelium; Testing; Transmembrane Transport; base; cell motility; innovation; insight; live cell imaging; mouse model; novel; photoreceptor disc

Project Summary A major function of the retinal pigment epithelium (RPE) is to ingest and degrade outer segment disk membranes from the photoreceptor cells. This catabolic role in the turnover of the phototransductive disk membranes is essential for the viability of the photoreceptor cells. The efficiency by which this role is carried out is also important for the health of the RPE cells, with related defects leading to pathogenesis. The ingestion and maturation of the ensuing phagosomes is dependent upon motor protein activity. The proposed research focuses on understanding this motor protein activity and the interactions of phagosomes with endo-lysosomes. The approach will include high-speed, live-cell imaging analysis in order to elucidate the dynamics of underlying cellular and molecular mechanisms. In a series of studies, the function of the Usher 1B protein, MYO7A, and microtubule motors will thus be investigated, in order to provide a detailed understanding of how these motors move POS phagosomes in RPE cells, and how the resulting phagosome motility facilitates phagosome maturation. The results will provide a new level of understanding of a central function of the RPE, with high relevance to retinal aging and disease.

项目摘要 视网膜色素上皮（RPE）的主要功能是摄取和降解外节盘 感光细胞的膜。这种分解代谢在光传导盘的周转中的作用 膜对于光感受器细胞的生存力是必需的。这一角色的执行效率 对于RPE细胞的健康也很重要，相关缺陷导致发病。的 随后吞噬体的摄取和成熟依赖于运动蛋白活性。的 拟议的研究重点是了解这种运动蛋白的活性和吞噬体的相互作用 内溶体该方法将包括高速，活细胞成像分析，以阐明 潜在的细胞和分子机制的动力学。在一系列研究中， Usher 1B蛋白、MYO7A和微管马达将因此被研究，以提供详细的 了解这些马达如何在RPE细胞中移动POS吞噬体，以及由此产生的吞噬体如何 运动促进吞噬体成熟。研究结果将使人们对一个中心的 视网膜色素上皮的功能，与视网膜老化和疾病高度相关。