The Astrocyte Nexus: CX 43-Protein Interactions

描述（由申请人提供）：长距离细胞间通信 在星形胶质细胞中，大部分是由缝隙连接通道介导的， 这些离子和代谢物直接从一个细胞传递到下一个细胞。的孔 星形胶质细胞缝隙连接主要由差距连接蛋白形成 连接蛋白43.最近的证据表明，其他蛋白质与 Cx43在缝隙连接处，我们称这种大分子复合物为 联系我们假设Nexus组件可以调节 差距连接通道的特性，也可能在细胞内 信号转导为了验证这一假设，我们将确定 在星形胶质细胞和胶质细胞中与Cx43结合的其他蛋白质的特性 转染的细胞，实施高通量和定量方法， 识别新的Nexus蛋白，测量相互作用的强度， 用Cx43突变体和Cx43结合进行生理学实验 合作伙伴，以确定这种相互作用的功能后果。在 此外，该应用程序的主要目标是获得结构信息 关于Cx43的结构域，它们彼此相互作用， proteins.这些研究采用多学科方法，旨在探索 这是该领域的一个新概念，因此预计将导致新的 了解缝隙连接在神经系统中的作用， 其他地方

DESCRIPTION (provided by the applicant): Long range intercellular communication among astrocytes is in large part mediated by gap junction channels through which ions and metabolites pass directly from one cell to the next. The pore of astrocyte gap junctions is formed primarily of the gap junction protein connexin43. Recent evidence indicates that other proteins are associated with Cx43 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. In order to test this hypothesis, we will determine the identities of the other proteins that bind to Cx43 in astrocytes and in transfected cells, implement high throughput and quantitative methods to identify novel Nexus proteins, measure the strengths of interaction, and perform physiological experiments with Cx43 mutants and with Cx43 binding partners to determine the functional consequences of such interactions. In addition, a major goal of this application is to obtain structural information regarding domains of Cx43 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 roles that gap junctions play in the nervous system and elsewhere.