Cellular Noise Suppression by the Regulator of G Protein Signaling Sst2

G proteins and their associated receptors process information from a variety of environmental stimuli to induce appropriate cellular responses. Generally speaking, each cell in a population responds within defined limits, despite large variation in the expression of protein signaling components. The...

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Bibliographic Details
Published in:Molecular cell 2014-07, Vol.55 (1), p.85-96
Main Authors: Dixit, Gauri, Kelley, Joshua B., Houser, John R., Elston, Timothy C., Dohlman, Henrik G.
Format: Article
Language:English
Subjects:
cdc42 GTP-Binding Protein, Saccharomyces cerevisiae - metabolism
Cell Polarity
GTP-Binding Proteins - metabolism
GTPase-Activating Proteins - physiology
Pheromones - metabolism
Saccharomyces cerevisiae Proteins - physiology
Signal Transduction
Transcription, Genetic
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Summary:G proteins and their associated receptors process information from a variety of environmental stimuli to induce appropriate cellular responses. Generally speaking, each cell in a population responds within defined limits, despite large variation in the expression of protein signaling components. Therefore, we postulated that noise suppression is encoded within the signaling system. Using the yeast mating pathway as a model, we evaluated the ability of a regulator of G protein signaling (RGS) protein to suppress noise. We found that the RGS protein Sst2 limits variability in transcription and morphogenesis in response to pheromone stimulation. While signal suppression is a result of both the GAP (GTPase accelerating) and receptor binding functions of Sst2, noise suppression requires only the GAP activity. Taken together, our findings reveal a hitherto overlooked role of RGS proteins as noise suppressors and demonstrate an ability to uncouple signal and noise in a prototypical stimulus-response pathway. [Display omitted] •RGS-GAP activity suppresses variability in transcription and morphogenesis•RGS-GAP activity is required to maintain cell polarization and track a gradient•Noise in gene induction is dynamically regulated•Signal suppression and noise suppression can occur independently G protein GTPase-activating proteins (GAPs) serve as signal suppressors. Using single-cell analysis, Dixit et al. demonstrate that the GAP activity of Sst2 also functions as a noise filter that suppresses variability in transcription and morphogenesis.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2014.05.019