An atlas of protein-protein interactions across mouse tissues. Author Michael Skinnider, Nichollas Scott, Anna Prudova, Craig Kerr, Nikolay Stoynov, Greg Stacey, Queenie Chan, David Rattray, Jörg Gsponer, Leonard Foster Publication Year 2021 Type Journal Article 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 Journal Cell Volume 184 Issue 15 Pages 4073-4089.e17 Date Published 07/2021 ISSN Number 1097-4172 DOI 10.1016/j.cell.2021.06.003 Alternate Journal Cell PMID 34214469 PubMedGoogle ScholarBibTeXEndNote X3 XML