Data from: Single-cell profiling screen identifies microtubule-dependent reduction of variation in cell signaling

Populations of isogenic cells often respond coherently to signals, despite differences in protein abundance and cell state. Previously, we uncovered processes in the Saccharomyces cerevisiae pheromone response system (PRS) that reduced cell-to-cell variation in signal strength and cellular response. Here, we screened 1141 nonessential genes to identify 50 "variation genes". Most had distinct, separable effects on strength and variability of the signal, defining these quantities as genetically distinct “axes” of system behavior. Three genes affected cytoplasmic microtubule function. We used genetic and chemical perturbations to show that, without microtubules, signal is reduced but variability is unaffected, while, when microtubule function is perturbed, signal is sometimes lowered, but signal variability is always high. The variability caused by microtubule perturbations required the MAP kinase Fus3 and membrane-associated Ste5, which Fus3 binds to generate signal. Visualization of Ste5 localization dynamics demonstrated that microtubule-dependent processes stabilize Ste5 at the membrane signaling site. The fact that microtubule perturbations cause aberrant fate and polarity decisions in mammals suggests that microtubule-dependent signal stabilization might operate in metazoans.