Deactivation mechanisms of rod phototransduction

描述(申请人提供)：棒和棒中的光子吸收 视网膜的视锥细胞激活一连串的生化反应 (光传导级联)对光产生电响应。 级联的激活和停用最终限制了幅度 和被转换信号的动力学，因此灵敏度和时间 视觉的分辨率。这项研究的总体目标是了解 关闭完整小鼠光感受器中光反应的机制。 基因打靶技术将被用来操纵子集的功能 已被认为在失活的蛋白质中起关键作用的蛋白质 级联，以及由此引起的单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，我们将问： (1)产生及时和可重复的 视紫红质失活？(2)哪些蛋白质相互作用促进转导 和PDE在完整细胞中的失活，并正常地进行这种失活 速率限制响应恢复？以及(3)停用步骤(S)加快了哪些步骤 在光适应过程中？这项研究将有助于澄清以下方面的初步步骤 正常的视觉过程，以及出现的疾病的发病机制 由于失活失败，例如某些形式的视网膜色素变性 和小口病。更广泛地说，这些实验将提供洞察力 探讨G蛋白失活的机制，所有类型的细胞 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.