The Astrocyte Nexus: Cx43 Protein Interactions

星形胶质细胞关系：Cx43 蛋白质相互作用

• 批准号: 8995082
• 负责人: Eliana Scemes
• 金额: $ 15.1万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8995082
• 关键词: Acute; Applications Grants; Astrocytes; Basement membrane; Binding; Biological; Biological Assay; Blood - brain barrier anatomy; Brain; Brain region; CXCL12 gene; Cell Polarity; Cells; Coculture Techniques; Complex; Connexin 43; Connexins; Coupling; Cysteine; Data; Disease; Dystroglycan; Endothelial Cells; Endothelium; Exhibits; Gap Junctions; Genotype; Goals; Hydrostatic Pressure; Immunohistochemistry; In Vitro; Infarction; Inflammatory; Ions; Knockout Mice; Life; Link; Liquid substance; Macromolecular Complexes; Measures; Mediating; Membrane Proteins; Metabolic; Microscopy; Modeling; Molecular; Mus; Mutant Strains Mice; Pathology; Pattern; Perfusion; Permeability; Photobleaching; Physiological; Physiology; Post-Translational Protein Processing; Property; Proteins; Recovery; Recovery of Function; Reporting; Resolution; Role; SHH gene; Signal Transduction; Staining method; Stains; Stroke; Surface Plasmon Resonance; Techniques; Testing; Tight Junctions; Time; Ultrasonography; Vascular Endothelial Growth Factors; base; developmental genetics; immunocytochemistry; innovation; insight; intermolecular interaction; macrophage; mutant; protein complex; public health relevance; release factor; research study; scaffold; tissue fixing

 DESCRIPTION (provided by applicant): Gap junction-mediated intercellular ionic and metabolic coupling provides both homeostatic and signaling functions among astrocytes throughout the brain, and CNS pathology both results in and is caused by disruptions in astrocyte gap junction signaling. It is now well known that gap junction proteins (connexins) interact with other proteins, forming a molecular complex we term the "Nexus". Recent data indicate that Nexus is a highly dynamic signaling unit, where direct linkages of connexins to adaptor and scaffolding molecules are bound to cytoskeletal, cytoplasmic and other membrane proteins, polarizing the astrocyte. The overall goal of this grant proposal is to understand how gap junctions in astrocytes control organization of this endfoot complex and thus control blood-brain-barrier integrity. To accomplish this goal, we propose to: Aim 1: Test the hypothesis that localization and mobility of gap junction proteins and their binding partners determines organization of astrocyte endfeet. Aim 2. Determine downstream effects of connexins on endothelial tight junction formation. Aim 3. Validate the hypothesis that localization and mobility of gap junction proteins and their binding partners determines organization of astrocyte endfeet using mice with modified connexin expression We believe that these interdisciplinary and innovative studies will provide the first molecular insights into the role of the astrocyte Nexus i establishment of cell polarity and thus identify important astrocyte functions that can be targeted to reverse disorders of astrocyte polarity.

 描述（由适用提供）：间隙连接介导的细胞间离子和代谢耦合提供整个大脑中星形胶质细胞之间的稳态和信号传导功能，而CNS病理学都会导致并且由星形胶质细胞间隙连接信号的中断引起并引起。现在众所周知，间隙连接蛋白（连接素）与其他蛋白质相互作用，形成了分子复合物，我们称为“ Nexus”。最近的数据表明Nexus是一个高度动态的信号单位，其中连接蛋白与衔接子和脚手架分子的直接连接与细胞骨架，细胞质和其他膜蛋白结合，使星形胶质细胞极化。该赠款提案的总体目标是了解该终脚复合体的星形胶质细胞控制组织中的间隙连接如何，从而控制了血脑屏障的完整性。为了实现这一目标，我们建议：目标1：测试差距连接蛋白及其结合伙伴的定位和移动性的假设决定了星形胶质细胞终端的组织。目标2。确定连接素对内皮紧密连接形成的下游影响。目标3。验证定位和流动性的假设 间隙连接蛋白及其结合伙伴的使用，确定使用具有修饰连接蛋白表达的小鼠的星形胶质细胞末端的组织，我们认为这些跨学科和创新的研究将提供第一个分子见解，以了解体形胶质细胞Nexus i Nexus i的作用，从而确定细胞极性的目标，从而识别出可以识别重要的星形磁体功能的功能 反向星形胶质细胞极性疾病。