Cellular Mechanisms of Photoreceptor Disk Morphogenesis

感光盘形态发生的细胞机制

• 批准号: 10442259
• 负责人: DAVID S WILLIAMS
• 金额: $ 45.89万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10442259
• 关键词: Address; Area; C-terminal; Cell membrane; Cells; Cellular biology; Cilia; Defect; Disease; Gatekeeping; Genetic study; Goals; Growth; Health; Human; Impairment; Knowledge; Length; Maintenance; Membrane; Methods; Microscopy; Molecular; Morphogenesis; Mus; Opsin; Pathogenesis; Pharmacology Study; Phenotype; Photoreceptors; Process; Proteins; Research; Resolution; Retinal Degeneration; Retinal Diseases; Rhodopsin; Role; Shapes; Site; Testing; Three-dimensional analysis; Tissues; Vertebrate Photoreceptors; Visual; experimental study; in vivo; novel; peripherin; photoreceptor disc; protein function; retinal rods; rho; tomography; tool

Project Summary The photoreceptor cilium is the most elaborate of all primary cilia. Its plasma membrane is extensively amplified to form a stack of disk membranes that contain a very high concentration of the visual receptor, opsin. This stack of disks forms the photoreceptor outer segment, and its organization is central to visual sensitivity and spatial resolution. The overall goal of the proposed research is to understand the cellular mechanisms involved in the morphogenesis of the disk membranes. The research plan is built on the application of molecular tools, with the use of advanced microscopy, including EM tomography and live-cell super-resolution microscopy, for high resolution, 3-D analysis. The long-term goal of the proposed research is to provide a molecular understanding of photoreceptor disk morphogenesis, including the mechanisms for delivering essential proteins to the site of membrane growth. The Specific Aims will address unknown aspects of the ciliary localization of opsin, and the roles of disk morphogenetic proteins in initiating lamellar growth, using both mouse rod photoreceptors in vivo and cultures of cells bearing unspecialized cilia. Our findings will provide understanding of a key area of photoreceptor cell biology. They will also be fundamental to our understanding of the pathogenesis of retinal disease that ensues from perturbations of disk membrane morphogenesis.

项目概要 光感受器纤毛是所有初级纤毛中最复杂的。其质膜广泛 放大形成一堆含有非常高浓度视觉受体的盘膜， 视蛋白。这堆圆盘形成了感光器的外节，其组织对于视觉至关重要 灵敏度和空间分辨率。拟议研究的总体目标是了解细胞 涉及盘膜形态发生的机制。 该研究计划建立在分子工具的应用基础上，利用先进的显微镜， 包括 EM 断层扫描和活细胞超分辨率显微镜，用于高分辨率 3D 分析。这 拟议研究的长期目标是提供对感光盘的分子理解 形态发生，包括将必需蛋白质递送至膜生长位点的机制。 具体目标将解决视蛋白纤毛定位的未知方面以及视盘的作用 形态发生蛋白在启动层状生长中使用小鼠视杆光感受器体内和 带有非特化纤毛的细胞培养物。我们的研究结果将提供对一个关键领域的理解 感光细胞生物学。它们也对于我们理解视网膜的发病机制至关重要。 由椎间盘膜形态发生扰动引起的疾病。