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.