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An Atlas of Protein-Protein Interactions Across Mouse Tissues

30 Pages Posted: 21 Jan 2021 Publication Status: Review Complete

See all articles by Michael A. Skinnider

Michael A. Skinnider

University of British Columbia (UBC) - Michael Smith Laboratories

Nicholas E. Scott

University of British Columbia (UBC) - Michael Smith Laboratories

Anna Prudova

University of British Columbia (UBC) - Michael Smith Laboratories

Craig H. Kerr

University of British Columbia (UBC) - Michael Smith Laboratories

Nikolay Stoynov

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology

Greg Stacey

University of British Columbia (UBC) - Michael Smith Laboratories

Queenie W.T. Chan

University of British Columbia (UBC) - Michael Smith Laboratories

David Rattray

University of British Columbia (UBC) - Michael Smith Laboratories

Joerg Gsponer

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology

Leonard J. Foster

University of British Columbia (UBC) - Michael Smith Laboratories

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Abstract

Cellular processes arise from the dynamic organization of proteins in networks of physical interactions. Mapping the complete interactome, has therefore been a central objective of high-throughput biology. However, interaction dynamics across physiological contexts remain poorly understood. Here, we combine protein correlation profiling with stable isotope labelling of mammals to map the interactomes of seven mouse tissues. The resulting maps provide the first proteome-scale survey of interactome dynamics across mammalian tissues, revealing over 125,000 unique interactions with an accuracy 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. Rewiring of protein interactions across tissues is widespread, and rewired proteins are tightly regulated by multiple cellular mechanisms and 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.

Suggested Citation

Skinnider, Michael A. and Scott, Nicholas E. and Prudova, Anna and Kerr, Craig H. and Stoynov, Nikolay and Stacey, Greg and Chan, Queenie W.T. and Rattray, David and Gsponer, Joerg and Foster, Leonard J., An Atlas of Protein-Protein Interactions Across Mouse Tissues. Available at SSRN: https://ssrn.com/abstract=3770938 or http://dx.doi.org/10.2139/ssrn.3770938
This version of the paper has not been formally peer reviewed.

Michael A. Skinnider

University of British Columbia (UBC) - Michael Smith Laboratories

Vancouver Campus
2185 East Mall
Vancouver, British Columbia V6T 1Z4
Canada

Nicholas E. Scott

University of British Columbia (UBC) - Michael Smith Laboratories ( email )

Vancouver Campus
2185 East Mall
Vancouver, British Columbia V6T 1Z4
Canada

Anna Prudova

University of British Columbia (UBC) - Michael Smith Laboratories

Vancouver Campus
2185 East Mall
Vancouver, British Columbia V6T 1Z4
Canada

Craig H. Kerr

University of British Columbia (UBC) - Michael Smith Laboratories

Vancouver Campus
2185 East Mall
Vancouver, British Columbia V6T 1Z4
Canada

Nikolay Stoynov

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology ( email )

Vancouver, British Columbia
Canada

Greg Stacey

University of British Columbia (UBC) - Michael Smith Laboratories ( email )

Vancouver Campus
2185 East Mall
Vancouver, British Columbia V6T 1Z4
Canada

Queenie W.T. Chan

University of British Columbia (UBC) - Michael Smith Laboratories

Vancouver Campus
2185 East Mall
Vancouver, British Columbia V6T 1Z4
Canada

David Rattray

University of British Columbia (UBC) - Michael Smith Laboratories ( email )

Vancouver Campus
2185 East Mall
Vancouver, British Columbia V6T 1Z4
Canada

Joerg Gsponer

University of British Columbia (UBC) - Department of Biochemistry and Molecular Biology ( email )

Vancouver, British Columbia
Canada

Leonard J. Foster (Contact Author)

University of British Columbia (UBC) - Michael Smith Laboratories ( email )

Vancouver Campus
2185 East Mall
Vancouver, British Columbia V6T 1Z4
Canada

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