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Nat Commun DOI:10.1038/s41467-021-22599-x

Proteomics of protein trafficking by in vivo tissue-specific labeling.

Publication TypeJournal Article
Year of Publication2021
AuthorsDroujinine, IA, Meyer, AS, Wang, D, Udeshi, ND, Hu, Y, Rocco, D, McMahon, JA, Yang, R, Guo, JJ, Mu, L, Carey, DK, Svinkina, T, Zeng, R, Branon, T, Tabatabai, A, Bosch, JA, Asara, JM, Ting, AY, Carr, SA, McMahon, AP, Perrimon, N
JournalNat Commun
Volume12
Issue1
Pages2382
Date Published2021 04 22
ISSN2041-1723
KeywordsAnimals, Animals, Genetically Modified, Biotin, Biotinylation, Carbon-Nitrogen Ligases, Cell Line, Disease Models, Animal, Drosophila, Embryonic Stem Cells, Escherichia coli Proteins, Female, Humans, Male, Mice, Protein Engineering, Protein Transport, Proteomics, Repressor Proteins, Staining and Labeling, Tandem Mass Spectrometry, Teratoma
Abstract

Conventional approaches to identify secreted factors that regulate homeostasis are limited in their abilities to identify the tissues/cells of origin and destination. We established a platform to identify secreted protein trafficking between organs using an engineered biotin ligase (BirA*G3) that biotinylates, promiscuously, proteins in a subcellular compartment of one tissue. Subsequently, biotinylated proteins are affinity-enriched and identified from distal organs using quantitative mass spectrometry. Applying this approach in Drosophila, we identify 51 muscle-secreted proteins from heads and 269 fat body-secreted proteins from legs/muscles, including CG2145 (human ortholog ENDOU) that binds directly to muscles and promotes activity. In addition, in mice, we identify 291 serum proteins secreted from conditional BirA*G3 embryo stem cell-derived teratomas, including low-abundance proteins with hormonal properties. Our findings indicate that the communication network of secreted proteins is vast. This approach has broad potential across different model systems to identify cell-specific secretomes and mediators of interorgan communication in health or disease.

DOI10.1038/s41467-021-22599-x
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/33888706?dopt=Abstract

Alternate JournalNat Commun
PubMed ID33888706
PubMed Central IDPMC8062696
Grant ListP41 GM132087 / GM / NIGMS NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States
R01 DK121409 / DK / NIDDK NIH HHS / United States
P01 CA120964 / CA / NCI NIH HHS / United States
P30 CA006516 / CA / NCI NIH HHS / United States