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An Atlas of Protein-Protein Interactions Across Mammalian Tissues

34 Pages Posted: 24 Jul 2018 Sneak Peek Status: Review Complete

See all articles by Michael A. Skinnider

Michael A. Skinnider

University of British Columbia (UBC) - Michael Smith Laboratories

Nichollas E. Scott

University of British Columbia (UBC) - Michael Smith Laboratories

Anna Prudova

University of British Columbia (UBC) - Michael Smith Laboratories

Nikolay Stoynov

University of British Columbia (UBC) - Michael Smith Laboratories

R. Greg Stacey

University of British Columbia (UBC) - Michael Smith Laboratories

Joerg Gsponer

University of British Columbia (UBC) - Michael Smith Laboratories

Leonard 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 network of biologically relevant protein-protein interactions, the interactome, has therefore been a central objective of high-throughput biology. Yet, because widely used methods for high-throughput interaction discovery rely on heterologous expression or genetically manipulated cell lines, the dynamics of protein interactions across physiological contexts are poorly understood. Here, we use a quantitative proteomic approach combining protein correlation profiling with stable isotope labelling of mammals (PCP–SILAM) 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 27,000 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 is poorly predicted by gene expression or coexpression. 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, Nichollas E. and Prudova, Anna and Stoynov, Nikolay and Stacey, R. Greg and Gsponer, Joerg and Foster, Leonard, An Atlas of Protein-Protein Interactions Across Mammalian Tissues (2018). Available at SSRN: https://ssrn.com/abstract=3219264 or http://dx.doi.org/10.2139/ssrn.3219264
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Michael A. Skinnider

University of British Columbia (UBC) - Michael Smith Laboratories

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

Nichollas E. Scott

University of British Columbia (UBC) - Michael Smith Laboratories

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

Nikolay Stoynov

University of British Columbia (UBC) - Michael Smith Laboratories

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

R. Greg Stacey

University of British Columbia (UBC) - Michael Smith Laboratories

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

Joerg Gsponer

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

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

Leonard 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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