Abstract：
In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins\' functions is unclear. Here, we use in situ proximity labeling to obtain the intracellular interactome of a teneurin (Ten-m) in the Drosophila brain. Genetic interaction studies using quantitative partner matching assays in both olfactory receptor neurons (ORNs) and projection neurons (PNs) reveal a common pathway: Ten-m binds to and negatively regulates a RhoGAP, thus activating the Rac1 small GTPases to promote synaptic partner matching. Developmental analyses with single-axon resolution identify the cellular mechanism of synaptic partner matching: Ten-m signaling promotes local F-actin levels and stabilizes ORN axon branches that contact partner PN dendrites. Combining spatial proteomics and high-resolution phenotypic analyses, this study advanced our understanding of both cellular and molecular mechanisms of synaptic partner matching.
摘要：
在发育大脑中，轴突在许多非伙伴细胞中选择突触伙伴时表现出惊人的精确度。进化保守的teneurin是指导突触伴侣匹配的跨膜蛋白。然而,细胞内信号通路如何执行teneurin的功能尚不清楚。这里,我们使用原位邻近标记来获得果蝇大脑中teneurin（Ten-m）的细胞内相互作用组。在嗅觉受体神经元（ORNs）和投射神经元（PNs）中使用定量伴侣匹配测定法进行的遗传相互作用研究揭示了一个共同的途径：Ten-m结合并负调节RhoGAP，从而激活Rac1小GTP酶促进突触伴侣匹配。具有单轴突分辨率的发育分析确定了突触伴侣匹配的细胞机制：Ten-m信号可促进局部F-肌动蛋白水平并稳定与伴侣PN树突接触的ORN轴突分支。结合空间蛋白质组学和高分辨率表型分析，这项研究提高了我们对突触伴侣匹配的细胞和分子机制的理解。
