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）的主要功能是摄入和降解外部段磁盘 来自感光细胞的膜。这种分解代谢在光转换磁盘的营业额中的作用 膜对于感光细胞的生存能力至关重要。携带此角色的效率 外出对于RPE细胞的健康也很重要，具有相关的缺陷导致发病机理。这 随后的吞噬体的摄入和成熟取决于运动蛋白活性。这 拟议的研究重点是理解这种运动蛋白活性和吞噬体的相互作用 带有内糖体。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， 因此，将研究USHER 1B蛋白，MyO7A和微管电机，以提供详细的 了解这些电动机如何移动RPE细胞中的POS吞噬体以及所得的吞噬体 运动促进吞噬体成熟。结果将为中心提供新的了解 RPE的功能，与视网膜衰老和疾病相关。