OPSINS, G PROTEIN PATHWAYS AND REGULATION IN RPE CELLS

RPE 细胞中的视蛋白、G 蛋白途径和调节

• 批准号: 2487834
• 负责人: HENRY K FONG
• 金额: $ 26.74万
• 依托单位: DOHENY EYE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2487834
• 关键词: G protein; circadian rhythms; gene expression; gene mutation; genetically modified animals; human tissue; immunocytochemistry; in situ hybridization; isomerase; laboratory mouse; laboratory rabbit; northern blottings; nucleic acid sequence; phospholipase C; protein binding; protein structure function; receptor coupling; retina disorder; retinal pigment epithelium; retinaldehyde; rhodopsin; tissue /cell culture; visual phototransduction; western blottings

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.

描述（改编自申请人的摘要）：脊椎动物 RPE 和 Muller 细胞含有一种细胞质视色素同系物，称为 RGR（RPE 视网膜G蛋白偶联受体）结合类维生素A并共享序列 与鱿鱼感光体中的一种光异构酶视黄色素相似。 该应用假设 RGR 可能充当视网膜异构酶 在脊椎动物的视觉周期中，参与原始形式的 光转导，在昼夜节律中发挥作用，或充当传感器 游离视黄醛。 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并分析所得表型 来自无 RGR 小鼠模型系统中 RGR 基因突变。 这 牛 RGR 的内源生色团将被鉴定并 与天然和重组 RGR 结合的视网膜的光异构化将是 调查了。 人类 RGR 基因的剪接变体称为 RGR-d 鉴定出其中预测的第六跨膜结构域被删除。 到 研究 RGR-d 与视网膜疾病有关的可能性 例如年龄相关性黄斑变性（AMD），研究将描述 人 RGR-d 视黄醛结合特性、亚细胞定位和 其他可能改变的属性。