Deactivation mechanisms of rod phototransduction

视杆光转导的失活机制

基本信息

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
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/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

项目摘要

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）：视网膜的视杆细胞和视锥细胞吸收光子会激活一系列生化反应（光转导级联），从而产生对光的电反应。级联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光感受器光反应的机制。基因靶向技术将用于操纵一部分蛋白质的功能，这些蛋白质在级联失活中发挥着关键作用，并且单杆细胞光响应的变化将通过电记录和蛋白质变化来确定通过实时 2 光子成像确定定位。使用这些方法，我们将解决三个重要问题：（1）视紫红质失活的时间过程是怎样的，以及它是如何由视紫红质激酶（GRK1）和视紫红质抑制蛋白（Arr1）之间的相互作用决定的？ (2) G*-E* 失活如何确定闪光响应的恢复，以及改变这种失活的速率如何通过突触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长期机制是什么？