Specialized junctions in the development of epithelia and neural circuits

上皮细胞和神经回路发育中的特殊连接

• 批准号: 10040885
• 负责人: Jessica E Treisman
• 金额: $ 21.19万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10040885
• 关键词: Abnormal Cell; Actins; Adherens Junction; Adhesions; Affect; Binding; Cell Adhesion; Cell Adhesion Molecules; Cell Communication; Cells; Chickens; Complex; Dendrites; Detection; Development; Diffusion; Disease; Drosophila genus; Epithelial; Epithelial Cells; Epithelium; Family member; Gastrointestinal tract structure; Genetic Diseases; Geometry; Goals; Homologous Gene; Immunoglobulins; Inflammatory Bowel Diseases; Intercellular Junctions; Interneurons; Invertebrates; Investigation; Kidney; Knowledge; Learning; Link; Location; Maintenance; Mechanics; Mediating; Microfilaments; Microscopy; Nature; Neoplasm Metastasis; Nervous system structure; Neurons; Organ; PDZ protein; Phase; Population; Proteins; Research; Retina; Role; Septate; Skin; Structure; Synapses; System; Testing; Tight Junctions; Time; Tissues; Visual Motion; Visual system structure; Yeasts; afadin; autism spectrum disorder; developmental disease; improved; insight; neural circuit; presynaptic; recruit; screening; seal; solute; synaptogenesis; three dimensional structure; tumor; yeast two hybrid system

Summary Adhesion between cells is important for the development of both epithelial tissues and neural circuits, and a growing number of adhesion molecules have been found to act in both contexts. For example, Sidekicks (Sdks) are immunoglobulin family members that mediate adhesion between specific synaptic partners in the vertebrate retina. Drosophila Sdk was recently shown to act as a hub for the assembly of tricellular adherens junctions (tAJs), which control tension at points where three epithelial cells meet, in addition to its function in the visual motion detection circuit. This proposal will investigate the mechanisms of Sdk localization and function in both contexts and explore possible connections between them. The first aim will investigate whether the localization of Sdk to tAJs is driven by the fit between its three-dimensional structure and their geometry. Sdk has been shown to recruit Polychaetoid and Canoe, which anchor the ends of actin filaments, to tAJs. However, Sdk can also interact with the WAVE regulatory complex, which promotes actin branching. The hypothesis that this interaction underlies the effect of Sdk on junction lengthening, while Polychaetoid and Canoe promote junction shortening, will be tested. A yeast two-hybrid screen will be used to identify additional factors that are recruited to tAJs by Sdk. The second aim will examine the synaptic localization of Sdk in the visual system. Expansion microscopy will be used to determine whether Sdk localizes to specific subregions of synapses between the Tm9 and T5 neurons, and/or to a specific location on T5 dendrites. The effect on Sdk localization of structural alterations in the protein and of tension in T5 will be tested. Finally, the possibility that epithelial interaction partners of Sdk also colocalize and function with it at synapses will be investigated. This exploratory proposal will provide insight into the assembly and function of the newly discovered tAJs, and may reveal a parallel structure at synapses. Identifying the common features of epithelial and synaptic junctions will contribute to our understanding of developmental disorders that affect either or both tissue types.

总结