Abstract
BackgroundThe yeast Saccharomyces cerevisiae relies on the high-osmolarity glycerol (HOG) signaling pathway to respond to increases in external osmolarity. The HOG pathway is rapidly activated under conditions of elevated osmolarity and regulates transcriptional and metabolic changes within the cell. Under normal growth conditions, however, a three-component phospho-relay consisting of the histidine kinase Sln1, the transfer protein Ypd1, and the response regulator Ssk1 represses HOG pathway activity by phosphorylation of Ssk1. This inhibition of the HOG pathway is essential for cellular fitness in normal osmolarity. Nevertheless, the extent to and mechanisms by which inhibition is robust to fluctuations in the concentrations of the phospho-relay components has received little attention.ResultsWe established that the Sln1-Ypd1-Ssk1 phospho-relay is robust—it is able to maintain inhibition of the HOG pathway even after significant changes in the levels of its three components. We then developed a biochemically realistic mathematical model of the phospho-relay, which suggested that robustness is due to buffering by a large excess pool of Ypd1. We confirmed experimentally that depletion of the Ypd1 pool results in inappropriate activation of the HOG pathway.ConclusionsWe identified buffering by an intermediate component in excess as a novel mechanism through which a phospho-relay can achieve robustness. This buffering requires multiple components and is therefore unavailable to two-component systems, suggesting one important advantage of multi-component relays.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-015-0158-y) contains supplementary material, which is available to authorized users.
Highlights
The yeast Saccharomyces cerevisiae relies on the high-osmolarity glycerol (HOG) signaling pathway to respond to increases in external osmolarity
We found that the phospho-relay maintains inactivation of the HOG pathway even after moderate perturbation of Sln1, Ypd1, and Ssk1
A theoretical analysis suggested that a large pool of the intermediate component Ypd1 can buffer fluctuations in other pathway components to maintain robustness
Summary
The yeast Saccharomyces cerevisiae relies on the high-osmolarity glycerol (HOG) signaling pathway to respond to increases in external osmolarity. A three-component phospho-relay consisting of the histidine kinase Sln, the transfer protein Ypd, and the response regulator Ssk represses HOG pathway activity by phosphorylation of Ssk. A three-component phospho-relay consisting of the histidine kinase Sln, the transfer protein Ypd, and the response regulator Ssk represses HOG pathway activity by phosphorylation of Ssk1 This inhibition of the HOG pathway is essential for cellular fitness in normal osmolarity. The high-osmolarity glycerol (HOG) pathway (Figure 1) of the budding yeast Saccharomyces cerevisiae mediates cellular response to increased external osmolarity [1,2]. The Sln1-Ypd1-Ssk three-component phospho-relay is responsible for maintaining inactivation of the HOG pathway under normal conditions.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have