@article{8c990ec29c9e4a4ebca785f226d055a6,
title = "An atlas of protein-protein interactions across mouse tissues",
abstract = "Cellular processes arise from the dynamic organization of proteins in networks of physical interactions. Mapping the interactome has therefore been a central objective of high-throughput biology. However, the dynamics of protein interactions across physiological contexts remain poorly understood. Here, we develop a quantitative proteomic approach combining protein correlation profiling with stable isotope labeling of mammals (PCP-SILAM) to map the interactomes of seven mouse tissues. The resulting maps provide a proteome-scale survey of interactome rewiring across mammalian tissues, revealing more than 125,000 unique interactions at a quality comparable to the highest-quality human screens. We identify systematic suppression of cross-talk between the evolutionarily ancient housekeeping interactome and younger, tissue-specific modules. Rewired proteins are tightly regulated by multiple cellular mechanisms and are implicated in disease. Our study opens up new avenues to uncover regulatory mechanisms that shape in vivo interactome responses to physiological and pathophysiological stimuli in mammalian systems.",
keywords = "co-fractionation mass spectrometry, mass spectrometry, network biology, protein correlation profiling, protein-protein interactions, proteomics",
author = "Skinnider, {Michael A.} and Scott, {Nichollas E.} and Anna Prudova and Kerr, {Craig H.} and Nikolay Stoynov and Stacey, {R. Greg} and Chan, {Queenie W.T.} and David Rattray and J{\"o}rg Gsponer and Foster, {Leonard J.}",
note = "Funding Information: This work was supported by funding from Genome Canada and Genome British Columbia (projects 214PRO and 264PRO to L.J.F.) and the Canadian Institutes of Health Research (MOP77688 to L.J.F.), and by computational resources provided by WestGrid Compute Canada, and Advanced Research Computing at the University of British Columbia. M.A.S. acknowledges support from a CIHR Vanier Canada Graduate Scholarship, an Izaak Walton Killam Memorial Pre-Doctoral Fellowship, a UBC Four Year Fellowship, and a Vancouver Coastal Health–CIHR–UBC MD/PhD Studentship. N.E.S. was supported by a Michael Smith Foundation Post-doctoral Fellowship (award #5363) and a National Health and Medical Research Council of Australia (NHMRC) Overseas (Biomedical) Fellow (APP1037373). The authors thank Alison McAfee for constructive comments on the manuscript, Dmitry Vavilov for assistance with the web server, and the Melbourne Mass Spectrometry and Proteomics Facility of the Bio21 Molecular Science and Biotechnology Institute at the University of Melbourne for mass spectrometry support. Conceptualization, M.A.S. N.E.S. J.G. and L.J.F.; methodology, M.A.S. N.E.S. A.P. C.H.K. R.G.S. J.G. and L.J.F.; formal analysis, M.A.S. N.E.S. R.G.S.; investigation, N.E.S. A.P. C.H.K. N.S. Q.W.T.C. and D.R.; writing – original draft, M.A.S. N.E.S. J.G. and L.J.F.; writing – review & editing, M.A.S. N.E.S. A.P. C.H.K. N.S. R.G.S. J.G. and L.J.F.; funding acquisition, L.J.F.; supervision, J.G. and L.J.F. The authors declare no competing interests. Funding Information: This work was supported by funding from Genome Canada and Genome British Columbia (projects 214PRO and 264PRO to L.J.F.) and the Canadian Institutes of Health Research ( MOP77688 to L.J.F.), and by computational resources provided by WestGrid Compute Canada , and Advanced Research Computing at the University of British Columbia . M.A.S. acknowledges support from a CIHR Vanier Canada Graduate Scholarship , an Izaak Walton Killam Memorial Pre-Doctoral Fellowship , a UBC Four Year Fellowship , and a Vancouver Coastal Health–CIHR–UBC MD/PhD Studentship . N.E.S. was supported by a Michael Smith Foundation Post-doctoral Fellowship (award # 5363 ) and a National Health and Medical Research Council of Australia (NHMRC) Overseas (Biomedical) Fellow (APP1037373). The authors thank Alison McAfee for constructive comments on the manuscript, Dmitry Vavilov for assistance with the web server, and the Melbourne Mass Spectrometry and Proteomics Facility of the Bio21 Molecular Science and Biotechnology Institute at the University of Melbourne for mass spectrometry support. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = jul,
day = "22",
doi = "10.1016/j.cell.2021.06.003",
language = "English (US)",
volume = "184",
pages = "4073--4089.e17",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "15",
}