TRANSDUCIN INACTIVATION AND ROD LIGHT ADAPTATION

拟议研究的目标是确定新的机制， 视觉感受器中的光传导和适应过程。 的 主要的焦点是确定转导蛋白GT3的生理作用 调节光反应的信使。 这项建议是根据 最近发现cGMP磷酸二酯酶，特别是其γ- 亚基，可以加速转导蛋白GT3活性， cGMP结合到非催化位点， 磷酸二酯酶α和β亚单位抑制GT3 加速度 这表明cGMP不仅是兴奋性信使 但也可以调节光传导的持续时间， 通过反馈机制的光反应。 第一个目标是 催化cGMP结合位点负责GT3调节， 定义cGMP从这些位点解离的项目量表 会导致GTTT加速。 这将表明cGMP- 依赖性抑制转导蛋白GT3是参与 在从单一光反应或/和光感受器适应的恢复中 到背景照明。 第二个目标是量化 磷酸二酯酶激活-失活循环的描述 结合到非催化位点的cGMP的存在和不存在。 的 所获得的参数将与GT3转导率相关 在相同条件下测量。 这种相关性将表明 磷酸二酯酶关闭是否仅由转导素GT3决定 或者涉及额外的机制。 第三个目标是确定 加速度的表位。 这部分工作的长期目标 是通过效应子寻找不同G蛋白的活性。 的 提出的实验与理解复杂的反馈有关， 调节光感受器活性的控制， 患有几种遗传性视网膜疾病。

The goal of the proposed study is to define new mechanisms regulating the phototransduction and adaptation processes in visual receptors. The major focus is to determine the physiological role of transducin GTPase regulation messenger in the photoresponse. This proposal is based on the recent finding that cGMP phosphodiesterase, specifically its gamma- subunit, can accelerate the GTPase activity of that transducin which activates it. cGMP binding to the non-catalytic sites of phosphodiesterase alpha and beta subunits suppresses the GTPase acceleration. This suggests that cGMP is not only a excitatory messenger in phototransduction but may also regulate the duration of the photoresponse through a feedback mechanism. The first aim of this catalytic cGMP-binding sites are responsible for GTPase regulation and to define the item scale on which cGMP dissociation from these sites causes GTPase acceleration. This will indicate whether the cGMP- dependent suppression of transducin GTPase is a candidate for involvement in recovery rom the single photoresponse or/and photoreceptor adaptation to background illumination. The second aim is to make a quantitative description of the phosphodiesterase activation-inactivation cycle in the presence and absence of cGMP bound to the non-catalytic sites. The obtained parameters will be correlated with the rate of transducin GTPase measured under the same conditions. This correlation will indicate whether phosphodiesterase turnoff is determine only by transducin GTPase or additional mechanisms are involved. The third aim is to determine the epitope on the acceleration. The long-term goal of this part of the work is to look for activity in different G-proteins by their effectors. The experiments proposed are relevant to understanding the intricate feedback controls that regulate photoreceptor activity, controls that may be perturbed in several inherited retinal diseases.