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.

项目摘要 光感受器纤毛是所有原发性纤毛中最精致的。它的质膜广泛 放大以形成一堆磁盘膜，其中包含非常高的视觉受体， OPSIN。这组磁盘构成了光感受器的外部细分市场，其组织对于视觉是核心 灵敏度和空间分辨率。拟议研究的总体目标是了解细胞 磁盘膜形态发生涉及的机制。 该研究计划建立在分子工具的应用上，并使用高级显微镜， 包括EM断层扫描和实时细胞超分辨率显微镜，用于高分辨率，3-D分析。这 拟议的研究的长期目标是提供对光感受器磁盘的分子理解 形态发生，包括向膜生长部位输送必需蛋白质的机制。 具体的目的将解决Opsin睫状定位的未知方面，以及磁盘的作用 形态发生蛋白在启动层状生长时使用小鼠杆杆感光体在体内和 带有无专门纤毛的细胞培养物。我们的发现将提供对关键领域的理解 感光细胞生物学。它们也将是我们对视网膜发病机理的理解至关重要的 椎间盘膜形态发生的扰动所带来的疾病。