OPSINS, G PROTEIN PATHWAYS AND REGULATION IN RPE CELLS

描述(改编自申请者摘要)：脊椎动物RPE和Muller 细胞含有一种称为RGR(代表RPE)的细胞质视觉色素同源物 视网膜G蛋白偶联受体)，与维甲酸结合并共享序列 与乌贼光感受器中的一种光异构酶-视黄素相似。 这一应用假设RGR可能作为视网膜异构酶发挥作用 在脊椎动物的视觉周期中，参与了原始形式的 光转导，在昼夜节律中起作用，或作为一种传感器 游离维A醛。为了检验这些假设，研究人员将调查RGR 配体和蛋白质结合特性及表型分析 在RGR缺失的小鼠模型系统中RGR基因的突变。这个 将鉴定牛RGR的内源发色团并 与天然和重组RGR结合的视网膜光异构化将被 调查过了。人类RGR基因的一种剪接变体被称为RGR-d 确定其中预测的第六跨膜结构域被删除。至 研究RGR-d参与视网膜疾病的可能性 例如老年性黄斑变性(AMD)，研究将表征 人RGR-d视黄醛结合特性及其亚细胞定位 其他可能被更改的财产。

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.