Deactivation mechanisms of rod phototransduction

视杆光转导的失活机制

• 批准号: 8327974
• 负责人: MARIE E BURNS
• 金额: $ 38.5万
• 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/8327974
• 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; Night Blindness; 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

DESCRIPTION (provided by applicant): 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?

描述（由申请人提供）：视网膜的棒和锥中光子的吸收会激活一系列生化反应（光转传级联），该反应产生了对光的电气反应。级联反应的激活和失活最终限制了转导信号的幅度和动力学，从而限制了视觉的灵敏度和时间分辨率。这项研究的总体目标是了解关闭完整小鼠感光体中光反应的机制。基因靶向技术将用于操纵一部分蛋白质的功能，这些蛋白质被认为在级联反应中起关键作用，并且将通过电气记录和由实时2 photon Image确定的蛋白质定位确定的单杆细胞的光呼应所致的变化。使用这些方法，我们将解决三个重要的问题：（1）视紫红质停用的时间过程是什么，以及如何通过视紫红质激酶（GRK1）（GRK1）和抑制蛋白（ARR1）之间的相互作用来确定它？ （2）g* -e*停用如何确定闪存响应的恢复，如何改变这种停用的速度在突触中传递以影响视觉功能？ （3）改变光响应失活动力学的光适应的持久机制是什么？