@article {1654484,
	title = {A genetic model for in vivo proximity labelling of the mammalian secretome},
	journal = {Open Biology},
	volume = {12},
	number = {8},
	year = {2022},
	month = {2022 08},
	pages = {220149},
	abstract = {Organ functions are highly specialized and interdependent. Secreted factors regulate organ development and mediate homeostasis through serum trafficking and inter-organ communication. Enzyme-catalysed proximity labelling enables the identification of proteins within a specific cellular compartment. Here, we report a BirA*G3 mouse strain that enables CRE-dependent promiscuous biotinylation of proteins trafficking through the endoplasmic reticulum. When broadly activated throughout the mouse, widespread labelling of proteins was observed within the secretory pathway. Streptavidin affinity purification and peptide mapping by quantitative mass spectrometry (MS) proteomics revealed organ-specific secretory profiles and serum trafficking. As expected, secretory proteomes were highly enriched for signal peptide-containing proteins, highlighting both 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 BirA*G3 mouse model demonstrates enhanced labelling efficiency and tissue specificity over viral transduction approaches and will facilitate a deeper understanding of secretory protein interplay in development, and in healthy and diseased adult states.},
	keywords = {Animals, Biotinylation, Mammals, Mass Spectrometry, Mice, Models, Genetic, Proteomics, Secretome},
	issn = {2046-2441},
	doi = {10.1098/rsob.220149},
	author = {Yang, Rui and Meyer, Amanda S and Droujinine, Ilia A and Udeshi, Namrata D and Hu, Yanhui and Guo, JinJin and McMahon, Jill A and Carey, Dominique K and Xu, Charles and Fang, Qiao and Sha, Jihui and Qin, Shishang and Rocco, David and Wohlschlegel, James and Ting, Alice Y and Carr, Steven A and Perrimon, Norbert and McMahon, Andrew P}
}
