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Mol Syst Biol 2018 May 14;145:e7997. doi: 10.15252/msb.20177997.
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Expression variation and covariation impair analog and enable binary signaling control.

Kovary KM , Taylor B , Zhao ML , Teruel MN .

Due to noise in the synthesis and degradation of proteins, the concentrations of individual vertebrate signaling proteins were estimated to vary with a coefficient of variation (CV) of approximately 25% between cells. Such high variation is beneficial for population-level regulation of cell functions but abolishes accurate single-cell signal transmission. Here, we measure cell-to-cell variability of relative protein abundance using quantitative proteomics of individual Xenopus laevis eggs and cultured human cells and show that variation is typically much lower, in the range of 5-15%, compatible with accurate single-cell transmission. Focusing on bimodal ERK signaling, we show that variation and covariation in MEK and ERK expression improves controllability of the percentage of activated cells, demonstrating how variation and covariation in expression enables population-level control of binary cell-fate decisions. Together, our study argues for a control principle whereby low expression variation enables accurate control of analog single-cell signaling, while increased variation, covariation, and numbers of pathway components are required to widen the stimulus range over which external inputs regulate binary cell activation to enable precise control of the fraction of activated cells in a population.

PubMed ID: 29759982
PMC ID: PMC5951153
Article link: Mol Syst Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: aurka aurkb ccna1 ccnb2 ccnk cdc6 cdk2 cdk5 egf eno1 mapk1 mcm4 mcm5 mcm7 notch1 pak2 plk1 raf1 ranbp1 siva1 srm ube2c

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References [+] :
Abell, Parallel adaptive feedback enhances reliability of the Ca2+ signaling system. 2011, Pubmed