美国斯坦福大学骆利群、Alice Y. Ting、Jiefu Li等研究人员合作利用果蝇大脑中的细胞表面蛋白组分析，揭示了神经元联结的调节因子。该项研究成果于2020年1月16日在线发表在《细胞》杂志上。

研究人员开发了一种特定于细胞类型的时空解析方法来分析完整组织中的细胞表面蛋白质组。蛹和成年果蝇嗅觉投射神经元（PN）细胞表面蛋白质组的定量分析揭示了从发育到成熟PN过渡过程中接线分子的整体下调和突触分子的上调。蛋白质组指导的体内筛选确定了20个调节神经回路装配的细胞表面分子，其中许多属于进化保守的蛋白家族，在以前的研究中没有发现与神经发育之间的联系。遗传分析进一步表明，脂蛋白受体LRP1细胞可自主控制PN树突的靶向作用，从而有助于形成精确的嗅觉图。这些发现凸显了时间分辨的原位细胞表面蛋白质组学谱分析在发现大脑连线调节因子中的作用。

据悉，在细胞界面上的分子相互作用介导了单细胞到组织的有序组装，并因此控制着多细胞生物的发育和生理。

附：英文原文

Title: Cell-Surface Proteomic Profiling in the Fly Brain Uncovers Wiring Regulators

Author: Jiefu Li, Shuo Han, Hongjie Li, Namrata D. Udeshi, Tanya Svinkina, D.R. Mani, Chuanyun Xu, Ricardo Guajardo, Qijing Xie, Tongchao Li, David J. Luginbuhl, Bing Wu, Colleen N. McLaughlin, Anthony Xie, Pornchai Kaewsapsak, Stephen R. Quake, Steven A. Carr, Alice Y. Ting, Liqun Luo

Issue&Volume: January 16, 2020

Abstract: Molecular interactions at the cellular interface mediate organized assembly of singlecells into tissues and, thus, govern the development and physiology of multicellularorganisms. Here, we developed a cell-type-specific, spatiotemporally resolved approachto profile cell-surface proteomes in intact tissues. Quantitative profiling of cell-surfaceproteomes of Drosophila olfactory projection neurons (PNs) in pupae and adults revealed global downregulationof wiring molecules and upregulation of synaptic molecules in the transition fromdeveloping to mature PNs. A proteome-instructed in vivo screen identified 20 cell-surface molecules regulating neural circuit assembly, manyof which belong to evolutionarily conserved protein families not previously linkedto neural development. Genetic analysis further revealed that the lipoprotein receptorLRP1 cell-autonomously controls PN dendrite targeting, contributing to the formationof a precise olfactory map. These findings highlight the power of temporally resolvedin situ cell-surface proteomic profiling in discovering regulators of brain wiring.

DOI: 10.1016/j.cell.2019.12.029

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31391-1