Regulation of Retinal Gap Junctions

由缝隙连接介导的电耦合有助于大多数类型的信号处理功能 视网膜神经元。视觉适应过程中缝隙连接的调节对敏感度和 许多神经元的感受场特性，并影响哺乳动物视杆细胞回路中的信号流路径。 这项研究的长期目标是确定调节大脑中电耦合的机制。 视网膜，并确定哪些调节模式对观察到的适应过程最重要 不同的电耦合神经电路。先前的研究结果表明，GAP的磷酸化 连接蛋白是调节偶联的重要机制。连接蛋白35/36(Cx35/36)的磷酸化 缝隙连接随着光的适应而动态变化，并与耦合直接相关。在这个项目中， 我们将研究通过Cx35/36 GAP控制耦合的截然不同的信号机制 所有无长突细胞和光感受器中的连接。我们将确定连接的关键分子成分 并解开这两个系统中的缝隙连接，并检查影响组装的因素 这些不同的信号模块。这项研究将阐明控制 电耦合，并揭示了在视觉障碍中可能存在缺陷的信号通路。

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.