An atlas of protein-protein interactions across mouse tissues

Michael A. Skinnider, Nichollas E. Scott, Anna Prudova, Craig H. Kerr, Nikolay Stoynov, R. Greg Stacey, Queenie W.T. Chan, David Rattray, Jörg Gsponer, Leonard J. Foster

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)4073-4089.e17
Issue number15
StatePublished - Jul 22 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


  • co-fractionation mass spectrometry
  • mass spectrometry
  • network biology
  • protein correlation profiling
  • protein-protein interactions
  • proteomics


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