MassIVE MSV000088848

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A genetic model for in vivo proximity labeling of the mammalian secretome

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Description

Yang R, Meyer AS, Droujinine I, Udeshi ND, Hu Y, Guo J, McMahon J, Carey DK, Xu C, Qiao F, Sha J, Qin S, Rocco D, Wohlschlegel J, Ting AY, Carr SA, Perrimon N, McMahon AP. 2022. Organ functions are highly specialized and interdependent. Tissue-specific secreted factors play a critical role in organ development, and homeostatic regulation, through serum trafficking and inter-organ communication. Enzyme-catalyzed proximity labeling is a powerful tool to label proteins within a specific cellular compartment. Here, we validated a BirA*G3 mouse strain enabling CRE-dependent promiscuous biotinylation of proteins within the endoplasmic reticulum. When intercrossed to a broadly active Sox2-Cre strain, widespread labeling of proteins was observed within the secretory pathway. Streptavidin affinity purification and peptide mapping by quantitative mass spectrometry (MS) revealed organ-specific secretory profiles and serum trafficking. As expected, secretory proteomes were highly enriched for signal peptide-containing proteins, and revealed conventional and non-conventional secretory processes, and ectodomain shedding. Lower-abundance proteins with hormone-like properties were recovered and validated using orthogonal approaches. Hepatocyte specific activation of BirA*G3 highlighted liver specific biotinylated secretome profiles. The model system will enhance an understanding of secretory protein interplay in development, and healthy and diseased adult states. [doi:10.25345/C5GS2J] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: TMT ; proximity labeling

Contact

Principal Investigators:
(in alphabetical order) 		Steven A. Carr, Broad Institute of MIT and Harvard, United States
Submitting User: clauser

Publications

Yang R, Meyer AS, Droujinine IA, Udeshi ND, Hu Y, Guo J, McMahon JA, Carey DK, Xu C, Fang Q, Sha J, Qin S, Rocco D, Wohlschlegel J, Ting AY, Carr SA, Perrimon N, McMahon AP.
A genetic model for in vivo proximity labelling of the mammalian secretome.
Open Biol. 2022 Aug;12(8):220149. Epub 2022 Aug 10.

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