RT Journal Article
SR Electronic
T1 An atlas of protein-protein interactions across mammalian tissues
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 351247
DO 10.1101/351247
A1 Michael A. Skinnider
A1 Nichollas E. Scott
A1 Anna Prudova
A1 Nikolay Stoynov
A1 R. Greg Stacey
A1 Joerg Gsponer
A1 Leonard J. Foster
YR 2018
UL http://biorxiv.org/content/early/2018/06/20/351247.abstract
AB 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.