Droujinine, I.A., Meyer, A.S., Wang, D., Udeshi, N.D., Hu, Y., Rocco, D., McMahon, J.A., Yang, R., Guo, J., Mu, L., Carey, D.K., Svinkina, T., Zeng, R., Branon, T., Tabatabai, A., Bosch, J.A., Asara, J.M., Ting, A.Y., Carr, S.A., McMahon, A.P., Perrimon, N. (2021). Proteomics of protein trafficking by in vivo tissue-specific labeling.  Nat. Commun. 12(1): 2382.

FBrf0248752

Research paper

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.

PMC8062696 (PMC) (EuropePMC)