OPSINS, G PROTEIN PATHWAYS AND REGULATION IN RPE CELLS

描述（改编自申请人摘要）：脊椎动物RPE和Muller 细胞含有称为RGR（对于RPE）的细胞质视色素同系物 视网膜G蛋白偶联受体）结合类维生素A并共享序列 与鱿鱼光感受器中的光异构酶视黄色素相似。 本申请假设RGR可能作为视网膜异构酶起作用 在脊椎动物的视觉周期中，涉及到一种原始形式的 光传导，在昼夜节律中发挥作用，或作为一种传感器， 游离视黄醇 为了验证这些假设，研究将调查RGR 配体和蛋白质结合特性，并分析表型 来自RGR-少小鼠模型系统中RGR基因的突变。 的 将鉴定牛RGR的内源性发色团， 结合到天然和重组RGR上的视黄醛的光异构化将是 研究了 人RGR基因的剪接变体称为RGR-d， 鉴定其中缺失预测的第六跨膜结构域。 到 研究RGR-d参与视网膜疾病的可能性 如年龄相关性黄斑变性（AMD），研究将描述 人RGR-d视黄酸去结合特性、亚细胞定位和 其他可能改变的属性。

DESCRIPTION (Adapted from applicant's abstract): Vertebrate RPE and Muller cells contain a cytoplasmic visual pigment homolog termed RGR (for RPE retinal G protein-coupled receptor) which binds retinoid and shares sequence similarity with retinochrome, a photoisomerase in squid photoreceptors. This application hypothesizes that RGR may function as a retinal isomerase in the vertebrate visual cycle, be involved in a primitive form of phototransduction, play a role in circadian rhythm, or act as a sensor of free retinaldehyde. To test these hypotheses, research will investigate RGR ligand- and protein-binding properties and analyze the phenotype resulting from mutation of the RGR gene in a RGR-less mouse model system. The endogenous chromophore of bovine RGR will be identified and photoisomerization of retinal bound to natural and recombinant RGR will be investigated. A splice variant of the human RGR gene termed RGR-d has been identified in which the predicted sixth transmembrane domain is deleted. To investigate the possibility that RGR-d is involved in diseases of the retina such as age-related macular degeneration (AMD), studies will characterize human RGR-d retinaldehyde-binding properties, subcellular localization and other possible altered properties.