ROD OUTER SEGMENTS

杆外段

• 批准号: 8361091
• 负责人: THEODORE G WENSEL
• 金额: $ 1.23万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361091
• 关键词: Cell membrane; Cells; Cilia; Defect; Disease; Electron Microscopy; Elements; Freeze Etching; Freezing; Funding; Genes; Goals; Grant; Human; Image; Lead; Location; Membrane; Microtubule Bundle; Mus; Mutation; National Center for Research Resources; Pathogenesis; Photoreceptors; Principal Investigator; Procedures; Research; Research Infrastructure; Resources; Retina; Retinal Degeneration; Retinal Diseases; Rhodopsin; Sampling; Source; Staining method; Stains; Structure; United States National Institutes of Health; cost; density; electron tomography; interest; macromolecule; mouse model

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal is to obtain three-dimensional images of photoreceptor cells and their internal structures from wildtype retinas and from retinas of mice with mutations corresponding to human retinal disease. Understanding these structures will help us to understand the normal structure of healthy photoreceptors, and the structural correlates of disease pathogenesis. The most interesting structures will be the disk membranes, flattened membrane sacks which fill up the photoreceptor outer segments. These are packed with rhodopsin at high density and the organization of rhodopsin in these membranes is a subject of considerable controversy. Disorganization of these membranes is observed in a number of mouse models of human retinal degeneration. We hope to see the structural organization of these membranes and their connections to cytoskeletal elements and the plasma membrane. These have been previously observed only in samples that have been sectioned and negatively stained, or subjected to freeze-etch procedures. Cryo-electron tomography offers the opportunity to observe these in intact cells (at least on the margins of the cell) with no manipulations other than rapid freezing. Also of interest will be the connecting cilium, a bundle of microtubules that connects the inner and outer segments and serves to transport outer segment components to their proper location. Defects in genes involved in the structure and function of this cilium and the trans-cilium transport also lead to retinal degeneration.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 目的是获得感光细胞及其内部的三维图像 来自野生型视网膜和小鼠视网膜的结构，其突变对应于 人类视网膜疾病。了解这些结构将帮助我们了解 健康感受器的正常结构和疾病的结构相关性 发病。最有趣的结构将是磁盘膜，变平 填充光感受器外部段的膜麻袋。这些包含 高密度下的视紫红质，在这些膜中的动蛋白的组织是一个受试者 有很大的争议。在许多人中观察到这些膜的混乱 人类视网膜变性的小鼠模型。我们希望看到 这些膜及其连接到细胞骨架元素和等离子体 膜。以前仅在已分割的样品中观察到这些 并受到负面染色或进行冻结程序。冷冻电子层析成像 提供了在完整的细胞中观察这些的机会（至少在细胞的边缘） 除了快速冻结之外，没有其他操作。同样感兴趣的是连接 Cilium，一束连接内部和外部段的微管 将外部细分部件运输到其适当的位置。涉及基因的缺陷 该纤毛的结构和功能和反式运输也导致了视网膜 退化。