Function of Photoreceptor Specific Cadherin

光感受器特异性钙粘蛋白的功能

• 批准号: 6746846
• 负责人: AMIR RATTNER
• 金额: $ 24.53万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6746846
• 关键词: Xenopus; biological signal transduction; cadherins; cytoplasm; gene expression; gene mutation; genetically modified animals; glycoprotein biosynthesis; immunoelectron microscopy; laboratory mouse; light microscopy; messenger RNA; molecular cloning; neurogenesis; protein localization; protein protein interaction; protein sequence; protein structure function; recombinant proteins; retina degeneration; rod cell; transfection; visual photoreceptor; zebrafish

DESCRIPTION (provided by applicant): The goal of this research program is to study the function of a novel photoreceptor specific cadherin (prCAD) that we recently identified. In our preliminary studies we showed that prCAD, a novel member of the cadherin family of cell adhesion proteins, is expressed only in retinal photoreceptors. We used immunoelectron microscopy to localize the prCAD protein to the margins of nascent membrane disks at the base of the photoreceptor outer segments (OS). We produced prCAD (-/-) mice and showed that in these mice the OS are disorganized and fragmented and there is progressive death of photoreceptor cells. The unique localization of prCAD to the base of the OS and the disrupted morphology of the OS in the mutant mice indicate an essential role for prCAD in the biosynthesis or maintenance of the outer segment. The prCAD (-/-) phenotype in the mouse and the high degree of conservation in the prCAD sequences between mice and humans predicts that mutations in human prCAD are likely to cause retinal diseases. We aim to (1) develop methods for expression of recombinant prCAD in photoreceptors of zebrafish and Xenopus to test the effect of mutations on the structure and function of this protein, (2) identify disease-associated mutations in human prCAD and study their function, (3) identify prCAD interacting proteins and study their role in outer segment morphogenesis, and (4) detect genes and signaling pathways that are differentially regulated in the prCAD (-/-) mouse retina.

描述（由申请人提供）：该研究计划的目的是研究我们最近确定的新型光感受器特异性钙粘蛋白（PRCAD）的功能。在我们的初步研究中，我们表明Prcad是细胞粘附蛋白的钙粘蛋白家族的新成员，仅在视网膜感受器中表达。我们使用免疫电子显微镜将prcad蛋白定位在光感受器外部段（OS）底部的新生膜盘的边缘。我们产生了PRCAD（ - / - ）小鼠，并表明在这些小鼠中，OS杂乱无章和分散，并且感光细胞会逐渐死亡。普卡德在OS底部的独特定位以及突变小鼠中OS的中断形态，这表明Prcad在外部片段的生物合成或维持中的重要作用。小鼠和人类之间的Prcad序列中的PRCAD（ - / - ）表型和人类之间的高度保守性预测，人Prcad中的突变可能会引起视网膜疾病。我们的目的是（1）开发用于表达斑马鱼和爪蟾光感受器中重组PRCAD的方法，以测试突变对该蛋白质的结构和功能的影响，（（2）鉴定与疾病相关的突变，并研究其功能，并研究其功能，（3）识别prcAD相互作用的蛋白质和差异性局部裂缝，并确定了外部片段的作用及其在外部片段和（4）的作用（4），（4）在（4）中（4））（4），（4）在（4）中，（4）在（4）中，（4））和（4）在（4）中（4），（4）在（4）中（4）识别它们的作用，（4））和（4）的作用（4）。在普卡德（ - / - ）小鼠视网膜中。