The Astrocyte Nexus: CX 43-Protein Interactions

星形胶质细胞关系：CX 43-蛋白质相互作用

• 批准号: 6621702
• 负责人: David C Spray
• 金额: $ 36.91万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-15 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621702
• 关键词: acid base balance; astrocytes; biological signal transduction; cell cell interaction; circular dichroism; computer simulation; electrophysiology; gap junctions; gel electrophoresis; immunoprecipitation; membrane channels; nuclear magnetic resonance spectroscopy; phosphorylation; protein binding; protein protein interaction; protein structure; proteomics; surface plasmon resonance; transcription factor; voltage /patch clamp; yeast two hybrid system

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.

描述（由申请人提供）：远程细胞间通信 在星形胶质细胞中，大部分是由间隙连接通道通过 哪个离子和代谢产物直接从一个细胞传递到另一个细胞。孔 星形胶质细胞间隙连接主要由间隙连接蛋白形成 connexin43。最近的证据表明其他蛋白质与 在间隙连接处的CX43，我们称这种大分子复合物 关系。我们假设Nexus组件可以调节 间隙连接通道的特性，也可能在细胞内发挥作用 信号转导。为了检验这一假设，我们将确定 在星形胶质细胞和中与CX43结合的其他蛋白质的身份 转染的单元，实施高吞吐量和定量方法 识别新型Nexus蛋白，测量相互作用的强度，并 用CX43突变体和CX43结合进行生理实验 确定这种相互作用的功能后果的合作伙伴。在 此外，此应用的主要目标是获取结构信息 关于彼此相互作用的CX43域 蛋白质。这些研究使用旨在探索的多学科方法 该领域的一个新概念，因此有望导致新颖 了解差距连接在神经系统中扮演的角色和 别处。