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

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
doi: https://doi.org/10.1101/819037
Jiefu Li
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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  • For correspondence: jiefuli@stanford.edu ayting@stanford.edu lluo@stanford.edu
Shuo Han
Departments of Genetics, Biology, and Chemistry, Chan Zuckerberg Biohub, Stanford University, Stanford, CA 94305, USA
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Hongjie Li
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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Namrata D. Udeshi
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Tanya Svinkina
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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D. R. Mani
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Chuanyun Xu
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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Ricardo Guajardo
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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Qijing Xie
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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Tongchao Li
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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David J. Luginbuhl
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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Bing Wu
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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Colleen N. McLaughlin
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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Anthony Xie
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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Pornchai Kaewsapsak
Departments of Genetics, Biology, and Chemistry, Chan Zuckerberg Biohub, Stanford University, Stanford, CA 94305, USA
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Stephen R. Quake
Departments of Bioengineering and Applied Physics, Chan Zuckerberg Biohub, Stanford University, Stanford, CA 94305, USA
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Steven A. Carr
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Alice Y. Ting
Departments of Genetics, Biology, and Chemistry, Chan Zuckerberg Biohub, Stanford University, Stanford, CA 94305, USA
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  • For correspondence: jiefuli@stanford.edu ayting@stanford.edu lluo@stanford.edu
Liqun Luo
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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  • For correspondence: jiefuli@stanford.edu ayting@stanford.edu lluo@stanford.edu
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SUMMARY

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 25, 2019.
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Cell-Surface Proteomic Profiling in the Fly Brain Uncovers New Wiring Regulators
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
bioRxiv 819037; doi: https://doi.org/10.1101/819037
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Cell-Surface Proteomic Profiling in the Fly Brain Uncovers New Wiring Regulators
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
bioRxiv 819037; doi: https://doi.org/10.1101/819037

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