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

Publication date: Available online 16 January 2020Source: CellAuthor(s): 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 LuoSummaryMolecular interactions at the cellular interface mediate organized assembly of single cells into tissues and, thus, govern the development and physiology of multicellular organisms. Here, we developed a cell-type-specific, spatiotemporally resolved approach to profile cell-surface proteomes in intact tissues. Quantitative profiling of cell-surface proteomes of Drosophila olfactory projection neurons (PNs) in pupae and adults revealed global downregulation of wiring molecules and upregulation of synaptic molecules in the transition from developing to mature PNs. A proteome-instructed in vivo screen identified 20 cell-surface molecules regulating neural circuit assembly, many of which belong to evolutionarily conserved protein families not previously linked to neural development. Genetic analysis further revealed that the lipoprotein receptor LRP1 cell-autonomously controls PN dendrite targeting, contributing to the formation of a precise olfactory map. These findings highlight the power of temporally resolved in situ cell-surface proteomic profiling in discovering regulators of brain wiring.Graphical Abstract
Source: Cell - Category: Cytology Source Type: research