Regulation of Retinal Gap Junctions

描述（由申请人提供）：由间隙连接介导的电耦合有助于大多数类型的视网膜神经元的信号处理功能。视觉适应过程中间隙连接的调节对许多神经元的敏感性和感受野特性有着深远的影响，并影响着哺乳动物视杆回路的信号流路径。本研究的长期目标是确定调节视网膜电耦合的机制，并确定哪种调节模式对不同电耦合神经回路中观察到的适应性过程最重要。先前的研究结果表明，间隙连接蛋白的磷酸化是调节偶联的关键机制。连接蛋白35/36 （Cx35/36）间隙连接的磷酸化随光适应动态变化，并与偶联直接相关。在这个项目中，我们将研究AII腺分泌细胞和光感受器中通过Cx35/36间隙连接控制耦合的不同信号传导机制。我们将确定在这两个系统中偶联和解耦间隙连接的关键分子成分，并检查有助于这些不同信号模块组装的因素。这项研究将揭示控制电耦合的基本机制，并揭示可能在视觉障碍中有缺陷的信号通路。

DESCRIPTION (provided by applicant): Electrical coupling mediated by gap junctions contributes to the signal processing functions of most types of retinal neurons. Modulation of gap junctions during visual adaptation has profound effects on sensitivity and receptive field properties of many neurons and influences the path of signal flow in the mammalian rod circuit. The long-term objectives of this study are to identify the mechanisms that regulate electrical coupling in the retina, and to determine which modes of regulation are most important for the adaptive processes observed in different electrically coupled neural circuits. Previous results have indicated that phosphorylation of gap junction proteins is a critical mechanism to regulate coupling. Phosphorylation of connexin 35/36 (Cx35/36) gap junctions changes dynamically with light adaptation and correlates directly with coupling. In this project, we will examine the profoundly different signaling mechanisms that control coupling through Cx35/36 gap junctions in AII amacrine cells and photoreceptors. We will identify the key molecular components that couple and uncouple the gap junctions in these two systems, and examine the factors that contribute to the assembly of these different signaling modules. This research will shed light on the fundamental mechanisms that control electrical coupling, and reveal signaling pathways that may be defective in visual disorders. PUBLIC HEALTH RELEVANCE: This project examines fundamental mechanisms that control cell-to-cell communication and the establishment of neural networks in the retina and throughout the central nervous system. It will reveal processes that play important roles in neural network functions that affect visual acuity and light adaptation, memory formation, and motor coordination. The study will reveal signaling pathways that may be targets for intervention in disorders linked to these network functions including macular degeneration, epilepsy, and hearing loss.