QUANTAL EVENTS IN VISUAL TRANSDUCTION

视觉传导中的量子事件

基本信息

批准号：
2668386
负责人：
DAVID W CORSON
金额：
$ 13.6万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-03-01 至 2000-02-29
项目状态：
已结题

项目摘要

The quantal response to a single photon is the elemental event in vision. In rods, this discrete electrical event results from activation of an enzyme cascade that closes hundreds of channels in the plasma membrane. Absorption of a photon normally initiates the process of photoexcitation by isomerization of the chromophore retinal from 11-cis to the all-trans configuration within the visual pigment, rhodopsin. After excitation, all- trans retinal is released from the apoprotein opsin, and ultimately replaced with fresh 11-cis retinal supplied by the pigment epithelium. The size and shape of the quantal response are governed by l) the intramolecular events which result in formation of Metarhodopsin II and the exposure of a catalytic binding site for transducin, a GTP-binding protein, 2) deactivation of Metarhodopsin II by phosphorylation of the carboxy terminus and capping by arrestin, 3) nearby molecules of photoactivated rhodopsin that produce background adaptation, 4) nearby molecules of opsin that produce opsin desensitization and 5) the availability of 11-cis retinal to convert opsin to its inactive rhodopsin configuration. The longterm objective of this investigation is to determine the mechanism(s) of retinoid uptake into photoreceptors and to gain a molecular explanation of the influence of the retinoids in the mechanisms of excitation and adaptation. As outlined in the progress report, work initiated in this laboratory has demonstrated that it is possible to manipulate excitation, adaptation and retinoid uptake with analogues of retinal. The Specific Aims of this proposal are to exploit these observations with an analysis of the physiological activities of selected analogues of retinal in intact cells. To this end, we propose: l) to determine the minimum structural requirements of retinal for the relief of opsin desensitization and for the control of excitation in rods & cones, 2) to identify the biochemical pathway responsible for opsin desensitization. 3) to determine the mechanism of retinoid uptake in rods and cones. The proposed work is addressed to program priorities of the NEI panel on Retinal and Choroidal Diseases. The work addresses fundamental mechanisms of receptor activation and desensitization with health ramifications relating to the efficacy of drugs and to the anomalies of pigment activation and dark adaptation associated with retinitis pigmentosa.

对单个光子的量子响应是视觉中的基本事件。在杆中，这种离散的电事件是由激活的关闭质膜中数百个通道的酶级联。光子的吸收通常会启动光激发过程通过将发色团视网膜从 11-顺式异构化为全反式视色素内的配置，视紫红质。激发后，所有 - 反式视网膜从脱辅基蛋白视蛋白中释放出来，最终替换为由色素上皮提供的新鲜 11-顺式视网膜。这量子响应的大小和形状由 l) 决定导致后视紫红质 II 形成的分子内事件转导蛋白（GTP 结合蛋白）催化结合位点的暴露蛋白，2) 通过磷酸化使后视紫红质 II 失活羧基末端并通过抑制蛋白封端，3) 附近的分子产生背景适应的光激活视紫红质，4) 附近产生视蛋白脱敏的视蛋白分子和 5) 11-顺式视网膜可将视蛋白转化为其无活性的视紫红质配置。这项调查的长期目标是确定类视黄醇摄取进入光感受器并获得光感受器的机制类维生素A影响机制的分子解释的激发和适应。正如进度报告中所述，工作该实验室发起的研究表明，有可能用类似物操纵兴奋、适应和类维生素A吸收视网膜。该提案的具体目标是利用这些观察并分析选定的生理活动完整细胞中的视网膜类似物。为此，我们建议： l) 确定视网膜的最低结构要求，以缓解视蛋白脱敏以及控制视杆细胞和视锥细胞的激发， 2) 确定负责视蛋白的生化途径脱敏。 3) 确定视杆细胞摄取类维生素A的机制和视锥细胞。拟议的工作针对 NEI 小组的计划优先事项视网膜和脉络膜疾病。这项工作涉及基本机制受体激活和脱敏对健康的影响与药物功效和色素异常有关与色素性视网膜炎相关的激活和暗适应。