Function and properties of the adhesion-G-protein-coupled receptor latrophilin in the fruit fly Drosophila melanogaster

本项目旨在研究亲和蛋白（latrophilins）的分子功能。亲和蛋白是一类单独的粘附- gpcr，在发育过程中参与突触神经传递和组织极化。迄今为止，尚不清楚嗜碱蛋白是否通过控制突触胞外事件、参与发育功能或其他途径在神经组织中发挥作用。最近在秀丽隐杆线虫（C. elegans）中获得的嗜水蛋白功能的研究结果揭示了嗜水蛋白在神经外胚层发育过程中的重要发育作用，并表明嗜水蛋白参与了原始极性的建立。亲乳蛋白在控制突触极性结构和功能性的建立或维持的机制中可能发挥的作用迄今尚未得到解决。在拟议的项目过程中，该假设将被测试果蝇黑腹果蝇的亲乳蛋白受体同源物是否参与眼睛和腹部表皮附属物和翅膀的组织极性的建立。其次，将研究在果蝇的神经肌肉连接处这一明确且特征明确的突触布局中去除嗜乳蛋白的影响。这组实验将解决嗜乳蛋白功能参与突触囊泡胞吐的假设。该项目的目标需要转基因果蝇菌株的产生、结构和超微结构显微镜、体内成像和高分辨率电生理学。

This project aims to investigate the molecular function of latrophilins, an individual class of adhesion-GPCRs, which are involved in synaptic neurotransmission and tissue polarization during development. To date it is unclear whether latrophilins exert their role in neural tissue by controlling synaptic exocytotic events, by participating in developmental functions, or by alternative means. Recent results on latrophilin function obtained in the roundworm C. elegans have uncovered essential developmental roles for latrophilins during neuroectodermal development and show that latrophilins partake in the establishment of primordial polarity. A possible role for latrophilins in mechanisms that govern the establishment or maintenance of structural and functional synaptic polarity has not been addressed to date. In the course of the proposed project the hypothesis will be tested whether the latrophilin receptor homolog of the fruitfly Drosophila melanogaster engages in the establishment tissue polarity ofthe eye and epidermal appendages ofthe abdomen and the wing. Secondly, the impact of latrophilin removal at a defined and well-characterized synaptic layout, the neuromuscular junction of Drosophila, will be investigated. This set of experiments will address the hypothesis that latrophilin function is involved in synaptic vesicle exocytosis. The project objectives require the generation of transgenic fly strains, structural and ultrastructural microscopy, in vivo imaging, and high-resolving electrophysiology.