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

Autor: Droujinine IA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. idroujinine@scripps.edu.; Department of Molecular Medicine, Scripps Research, La Jolla, CA, USA. idroujinine@scripps.edu., Meyer AS; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA, USA., Wang D; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.; Department of Entomology, China Agricultural University, Beijing, China., Udeshi ND; Broad Institute of Harvard and MIT, Cambridge, MA, USA., Hu Y; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Rocco D; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., McMahon JA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA, USA., Yang R; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA, USA., Guo J; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA, USA., Mu L; Department of Electrical Engineering, Yale University, New Haven, CT, USA., Carey DK; Broad Institute of Harvard and MIT, Cambridge, MA, USA., Svinkina T; Broad Institute of Harvard and MIT, Cambridge, MA, USA., Zeng R; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Branon T; Chan Zuckerberg Biohub, San Francisco, CA, USA., Tabatabai A; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Bosch JA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Asara JM; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA, USA., Ting AY; Chan Zuckerberg Biohub, San Francisco, CA, USA.; Departments of Genetics, Biology, and Chemistry, Stanford University, Stanford, CA, USA., Carr SA; Broad Institute of Harvard and MIT, Cambridge, MA, USA., McMahon AP; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA, USA., Perrimon N; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. perrimon@genetics.med.harvard.edu.; Howard Hughes Medical Institute, Boston, MA, USA. perrimon@genetics.med.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Apr 22; Vol. 12 (1), pp. 2382. Date of Electronic Publication: 2021 Apr 22.
DOI: 10.1038/s41467-021-22599-x
Abstrakt: 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.
Databáze: MEDLINE
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