Neuronal Gap Junctions: Cx36 Gating, Binding & Function

描述（由申请人提供）：神经元之间的电突触是 由间隙连接通道形成，离子和代谢物通过该通道 直接从一个细胞转移到另一个细胞最近的证据表明， 蛋白质与缝隙连接处的连接蛋白相关，我们称之为 这个大分子复合体，也就是“连接”我们假设Nexus组件 可以调节差距连接通道的性质，并且还可以 在细胞内信号转导中起作用。一种新的缝隙连接蛋白， 连接蛋白36，已被鉴定，其表达主要限于 神经元，我们已经表明，由这种连接蛋白形成的通道， 似乎是唯一适合它作为神经元连接蛋白的特性。的目标 这项授权申请是为了表征门控，渗透性和 电导特性与蛋白质结构域有关，以确定 脑和神经元裂解物中与连接蛋白36结合的其他蛋白质， 使用表面等离子体共振的相互作用的强度，并执行 对神经元样细胞进行生理学实验以确定Cx36的作用 表达对神经元分化和基因表达模式的影响。在 此外，该应用程序的主要目标是获得结构信息 使用光谱学方法，关于与每一个相互作用的Cx36的结构域， 和其他蛋白质。这些研究采用多学科方法 旨在探索该领域的新概念，因此预计将 导致对缝隙连接的调节和作用的新的理解， 神经系统

DESCRIPTION (provided by applicant): Electrical synapses between neurons are formed by gap junction channels, through which ions and metabolites pass directly from one cell to the next. Recent evidence indicates that other proteins are associated with connexins at gap junctions, and we have termed this macromolecular complex the Nexus. We hypothesize that the Nexus components may regulate both the properties of the gap junction channels and also may function in intracellular signal transduction. A new gap junction protein, connexin36, has been identified that is largely restricted in its expression to neurons, and we have shown that the channels formed by this connexin have properties that seem to uniquely suit it as a neuronal connexin. The goals of this grant application are to characterize the gating, permeability and conductance properties with regard to the protein domains involved, to identify other proteins in brain and neuron lysates that bind to connexin36, measure the strengths of interaction using surface plasmon resonance, and perform physiological experiments on neuron-like cells to determine the effects of Cx36 expression on neuronal differentiation and gene expression patterns. In addition, a major goal of this application is to obtain structural information using spectroscopic methods regarding domains of Cx36 that interact with each other and with other proteins. These studies use a multidisciplinary approach directed at exploring a new concept in the field and as such are expected to lead to novel understanding of regulation and roles of gap junctions in the nervous system.