Cellular Noise Suppression by the Regulator of G Protein Signaling Sst2

Abstract

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.

RGS Proteins and Septins Cooperate to Promote Chemotropism by Regulating Polar Cap Mobility

“…During chemotropic growth, the polar cap wanders back and forth across the growing edge of the cell, and this behavior is required for gradient tracking [29]. Given that Sst2 is also required for cells to track a gradient [3, 21] we considered the role of Sst2 in controlling the movement of the polar cap. We began by comparing the distribution of the polar cap in wild type cells and in mutant cells lacking Sst2 ( sst2 Δ).…”

“…We began by comparing the distribution of the polar cap in wild type cells and in mutant cells lacking Sst2 ( sst2 Δ). Experiments were performed in a custom-designed microfluidic device that produces a gradient across the cells [16, 21]. Using the microfluidic chamber, we exposed cells to a 0 to 150 nM gradient of pheromone and examined the localization of the Cdc42-GTP binding protein Bem1 over time [30, 31].…”

“…It binds to the pheromone receptor and also functions as a GTPase activating protein (GAP) for Gpa1 [19, 20]. Both functions contribute equally to desensitization of the pathway [21]. However it is the GAP activity alone that is required for proper gradient tracking [21].…”

“…Both functions contribute equally to desensitization of the pathway [21]. However it is the GAP activity alone that is required for proper gradient tracking [21]. …”

Composite macroH2A/NRF-1 Nucleosomes Suppress Noise and Generate Robustness in Gene Expression

“…Chromatin remodeling factors such as HDACs can decrease the frequency or size of transcriptional bursts , whereas nucleosome-disfavoring sequences can also limit noise by allowing a fine-tuned regulation of gene expression (Raveh-Sadka et al, 2012). Finally, cell-signaling pathways are embedded with noise-suppression components (Dixit et al, 2014;Shimizu et al, 2014). Together with these previous studies, our results strongly suggest that cells have evolved various noise-suppression mechanisms that work both in parallel and antagonistically with the molecular pathways that generate noise, thus ensuring the robustness and multiplicity of the responses.…”