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Cell. 2021 Jul 22;184(15):4073-4089.e17. doi: 10.1016/j.cell.2021.06.003. Epub 2021 Jul 01.

An atlas of protein-protein interactions across mouse tissues.

Cell

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

Affiliations

  1. Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
  2. Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Peter Doherty Institute, Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC 3000, Australia.
  3. Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  4. Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: [email protected].
  5. Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: [email protected].

PMID: 34214469 DOI: 10.1016/j.cell.2021.06.003

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.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: co-fractionation mass spectrometry; mass spectrometry; network biology; protein correlation profiling; protein-protein interactions; proteomics

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Publication Types

Grant support