美国斯坦福大学骆利群、李介夫等提出了突触配对中神经蛋白信号传导的分子和细胞机制。这一研究成果于2024年7月11日发表在国际顶尖学术期刊《细胞》上。
研究人员原位邻近标记法获得果蝇大脑中Teneurin（Ten-m）的细胞内互作组。研究人员利用定量伙伴匹配测定的基因互作研究，在嗅觉受体神经元（ORN）和投射神经元（PN）中揭示了一个共同的途径：Ten-m结合并负调控RhoGAP，从而激活Rac1小GTP酶以促进突触伙伴匹配。
通过单轴突分辨率的发育分析，确定了突触伙伴匹配的细胞机制：Ten-m信号传导促进了局部F-肌动蛋白水平，并稳定了接触到伙伴投射神经元树突的嗅觉受体神经元轴突分支。结合空间蛋白质组学和高分辨率表型分析，本研究推进了对突触伙伴匹配的细胞和分子机制的理解。
据介绍，在发育中的大脑中，轴突在许多非伴侣细胞中选择突触伴侣表现出非凡的精确性。进化上保守的teneurins是跨膜蛋白，指导突触伴侣匹配。然而，细胞内信号通路如何执行teneurins的功能尚不清楚。
附：英文原文
Title: Molecular and cellular mechanisms of teneurin signaling in synaptic partner matching
Author: Chuanyun Xu, Zhuoran Li, Cheng Lyu, Yixin Hu, Colleen N. McLaughlin, Kenneth Kin Lam Wong, Qijing Xie, David J. Luginbuhl, Hongjie Li, Namrata D. Udeshi, Tanya Svinkina, D.R. Mani, Shuo Han, Tongchao Li, Yang Li, Ricardo Guajardo, Alice Y. Ting, Steven A. Carr, Jiefu Li, Liqun Luo
Issue&Volume: 2024-07-11
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.
DOI: 10.1016/j.cell.2024.06.022
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00696-2