Deactivation mechanisms of rod phototransduction

描述（由申请人提供）：光子在棒中的吸收， 视网膜的视锥细胞激活了一连串的生化反应 （光传导级联），其产生对光的电响应。 级联的激活和去激活最终限制了振幅 和动力学的转导信号，因此灵敏度和时间 视觉的分辨率。本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个子集的功能 这些蛋白质被认为在细胞的失活中起着关键作用， 级联，以及由此产生的单视杆细胞光响应的变化 将通过电子记录来确定。使用这种方法，我们会问： (1)什么是产生及时和可复制的 视紫红质失活(2)什么样的蛋白质相互作用促进了转导 和PDE失活，这种失活通常 限速响应恢复？以及（3）加速了哪些去活化步骤 在适应光？这项研究将有助于澄清 正常的视觉过程，以及疾病的发病机制， 失活失败，例如某些形式的视网膜色素变性 和Oguchi病。更一般地说，这些实验将提供见解 G蛋白级联的失活机制，所有细胞类型 用于将细胞外信号转化为细胞内反应。

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 photo responses of single rod cells will be determined by electrical recording. Using this approach, we will ask: (1) What are the mechanisms that produce the timely and reproducible deactivation of rhodopsin? (2) What protein interactions facilitate transducin and PDE deactivation in intact cells, and does this deactivation normally rate-limit response recovery? and (3) What deactivation step(s) are speeded during light adaptation? This research will help clarify the initial steps in the normal visual process, as well as the pathogenesis of diseases that arise from failures of deactivation, such as in some forms of retinitis pigmentosa and Oguchi disease. More generally, these experiments will provide insights into the mechanisms of deactivation of G protein cascades, which all cell types use to transduce extracellular signals into intracellular responses.