Photoreceptor Membrane Guanylyl Cyclases

光感受器膜鸟苷酸环化酶

• 批准号: 6620092
• 负责人: JAMES Bryant HURLEY
• 金额: $ 37.44万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6620092
• 关键词: X ray crystallography; autosomal dominant trait; calcium binding protein; calcium ion; cyclic GMP; electrophysiology; electroretinography; enzyme biosynthesis; enzyme structure; fluorescent dye /probe; gene mutation; genetically modified animals; guanylate cyclase; laboratory mouse; light adaptations; membrane proteins; protein structure function; retina; retina degeneration; retinal adaptation; visual photoreceptor

DESCRIPTION (provided by applicant): Light adaptation is the ability of a photoreceptor to make biochemical adjustments that enable it to detect changes in illumination even in the presence of what would otherwise be a saturating stimulus. A cyclic GMP-mediated enzymatic pathway is used to detect light in rod and cone photoreceptors. One of the biochemical reactions that initiates light adaptation is a Ca2+-mediated feedback pathway that regulates synthesis of cyclic GMP by guanylyl cyclase. The aims of this application are to: (i) understand at a structural level how photoreceptor membrane guanylyl cyclases are regulated by Ca2+ and Ca2+-binding proteins; (ii) understand at the molecular level how mutations in a photoreceptor guanylyl cyclase cause a dominant degenerative disease of the retina, Autosomal Dominant Cone-Rod Dystrophy; and (iii) understand at the physiological level how regulation of cyclic GMP synthesis determines how a photoreceptor adapts to light and how well it returns to the dark state following illumination. These studies will provide fundamental information about how photoreceptors detect light and they will provide insights into the molecular basis of inherited diseases of the retina.

描述（由申请人提供）：光适应性是 光感受器进行生化调整，使其能够检测变化 即使在否则饱和的情况下，也有照明 刺激。循环GMP介导的酶途径用于检测光 杆和锥形感受器。发起的生化反应之一 光适应是一种CA2+介导的反馈途径，可调节合成 Guanylyl Cyclase的环状GMP。 该应用的目的是：（i）在结构层面上了解如何 受感受器膜鸟叶烯循环酶由Ca2+和Ca2+结合调节 蛋白质； （ii）在分子水平上了解如何突变 光感受器鸟叶酸环化酶引起的主要退化性疾病 视网膜，常染色体显性锥体杆营养不良症； （iii）在 生理级别的调节如何循环GMP合成决定了 光感受器适应光，又如何恢复到黑暗状态 照明。 这些研究将提供有关光感受器的基本信息 检测光，它们将提供有关分子基础的见解 视网膜的继承疾病。