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bioRxiv · 10.1101/244236

Expression variation and covariation impair analog and enable binary signaling control

Kovary, K. M.·Taylor, B.·Zhao, M. L.·Teruel, M. N.
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Abstract

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. This high variation enables 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. Furthermore, we show that MEK and ERK expression covary which improves controllability of the fraction of cells that activate bimodal ERK signaling, arguing that covariation has a role in facilitating population-level control of binary cell-fate decisions. Together, our experimental and model data argues for a control principle whereby low covariation limits signaling noise for accurate control analog single-cell signaling. In contrast, increased covariation widens the stimulus-range over which external inputs can regulate binary cell activation, thereby enabling accurate control of the fraction of activated cells at the population level.

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Kovary, K. M., Taylor, B., Zhao, M. L., Teruel, M. N.. 2018-01-08. Expression variation and covariation impair analog and enable binary signaling control. https://doi.org/10.1101/244236

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