Deactivation mechanisms of rod phototransduction

视杆光转导的失活机制

• 批准号: 8265252
• 负责人: MARIE E BURNS
• 金额: $ 51.33万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8265252
• 关键词: ARRB1 gene; Acceleration; Accounting; Address; Affect; Affinity; Arrestins; Behavioral; Behavioral Paradigm; Binding; Biochemical Reaction; Calcium; Cells; Code; Complex; Computer Simulation; Cyclic GMP; Dark Adaptation; Data; Diffusion; Disease; Electrodes; Electrophysiology (science); Eukaryotic Cell; Exposure to; Failure; Feedback; GRK1 gene; GTP-Binding Proteins; Gene Targeting; Goals; Image; Individual; Kinetics; Knowledge; Life; Light; Light Adaptations; Lighting; Membrane; Molecular; Mouse Strains; Movement; Mus; Pathogenesis; Phosphorylation; Photons; Photoreceptors; Phototransduction; Play; Property; Proteins; Recovery; Regulation; Reproducibility; Research; Resolution; Retina; Retinal; Retinal Cone; Retinal Diseases; Retinitis Pigmentosa; Rhodopsin; Running; Scheme; Signal Transduction; Speed; Stimulus; Suction; Synapses; Synaptic Transmission; System; Tail; Techniques; Testing; Time; Transgenic Mice; Transmembrane Domain; Vertebrate Photoreceptors; Vision; Visual; Work; absorption; analytical method; base; extracellular; guanylate cyclase activating protein; improved; insight; overexpression; programs; recoverin protein; relating to nervous system; research study; response; retinal rods; rhodopsin kinase; two-photon; visual adaptation; visual process; visual processing

Project Summary The absorption of photons in rods and cones of the retina activates a cascade of biochemical reactions (phototransduction cascade) that generates the electrical response to light. The activation and deactivation of the cascade ultimately limits the amplitude and kinetics of the transduced signal, and thus the sensitivity and temporal resolution of vision. The overall goal of this study is to understand the mechanisms that turn off the light response in intact mouse photoreceptors. Gene targeting techniques will be used to manipulate the function of a subset of proteins that have been suggested to play key roles in deactivation of the cascade, and the resulting changes in the photoresponses of single rod cells will be determined by electrical recording and changes in protein localization determined by real-time 2-photon imaging. Using these approaches, we will address three important questions: (1) What is the time course of rhodopsin deactivation, and how is it determined by the interactions between rhodopsin kinase (GRK1) and arrestin (Arr1)? (2) How does G*-E* deactivation determine recovery of the flash response, and how does changing the rate of this deactivation get relayed across the synapse to affect visual function? and (3) What are the long-lasting mechanisms of light adaptation that alter the kinetics of photoresponse deactivation?

项目摘要 视网膜的棒和锥中光子的吸收激活了生化的级联 产生对光的电响应的反应（光转传级联）。这 级联的激活和停用最终限制了振幅和动力学 转导信号，从而使视力的灵敏度和时间分辨率。总体目标 这项研究是了解关闭完整鼠标光响应的机制 感受器。基因靶向技术将用于操纵子集的功能 建议在级联反应中发挥关键作用的蛋白质， 导致单杆细胞的光子的变化将由电气确定 通过实时2光子成像确定的记录和蛋白质定位的变化。使用 这些方法，我们将解决三个重要问题：（1）时间课程是什么 视紫红质失活，以及如何取决于视紫红质激酶之间的相互作用 （grk1）和逮捕（ARR1）？ （2）g* -e*停用如何确定闪光灯的恢复 响应以及如何在突触中传递这种停用的速度 影响视觉功能？ （3）光适应的持久机制是什么 改变光响应失活的动力学？