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

ABSTRACT: Li J, Han S, Li H, Udeshi ND, Svinkina T, Mani DR, Xu C, Guajardo R, Xie Q, Li T, Luginbuhl DJ, Wu B, McLaughlin CN, Xie A, Kaewsapsak P, Quake sR, Carr SA, Ting AY, Luo L. 2019. Molecular 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 a global down-regulation of wiring molecules and an up-regulation of synaptic molecules in the transition from developing to mature PNs. A proteome-instructed in vivo screen identified 20 new 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 new regulators of brain wiring.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Drosophila <fruit Fly, Genus> (ncbitaxon:7215)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000084543 | MassIVE | Wed Nov 06 06:40:00 GMT 2019

REPOSITORIES: MassIVE

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