Deactivation mechanisms of rod phototransduction

视杆光转导的失活机制

基本信息

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
项目类别：
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

项目摘要

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?

项目概要视网膜的视杆细胞和视锥细胞吸收光子会激活一系列生化反应产生对光的电响应的反应（光转导级联）。这级联的激活和失活最终限制了级联的幅度和动力学转换的信号，从而提高视觉的灵敏度和时间分辨率。总体目标为这项研究旨在了解关闭完整小鼠的光反应的机制光感受器。基因打靶技术将用于操纵子集的功能已被认为在级联失活中发挥关键作用的蛋白质，以及单杆细胞光响应的变化将由电学决定通过实时 2 光子成像确定蛋白质定位的记录和变化。使用通过这些方法，我们将解决三个重要问题：（1）时间进程是多少？视紫红质失活，以及视紫红质激酶之间的相互作用是如何决定的 (GRK1) 和抑制蛋白 (Arr1)？ (2) G*-E*去激活如何判断flash的恢复响应，以及如何改变这种失活的速率通过突触传递影响视功能？ (3) 光适应的长期机制是什么？改变光响应失活的动力学？