EXTRA BUT NOT USELESS: SHARED AND REDUNDANT PROTEINS COORDINATE SIGNAL CROSS-TALK BETWEEN MAPK PATHWAYS IN YEAST

To survive, cells must sense and respond to an ever-changing environment. In doing so, each cell must detect, interpret and adapt to multiple and concurrent extracellular stimuli, such as a mixture of hormones and nutrients. While signaling pathways are highly specialized towards specific stimuli, different pathways often share components and in some cases use components that appear redundant. We propose that these shared components and redundancies help the cell to better coordinate signals for cell survival. In the yeast Saccharomyces cerevisiae, the mating and the high osmolarity glycerol (HOG) pathways are among the best-characterized. The HOG pathway has two seemingly redundant branches, mediated by Sln1 and Sho1. Either branch can be activated by high osmotic pressure which leads to the phosphorylation of the MAPKs Hog1 and Kss1, a pause in cell cycle progression, new transcription, and the production of osmolytes. The mating pathway is activated by pheromone, which leads to the phosphorylation of the MAPKs Fus3 and Kss1, arrest in G1, new transcription, and cell fusion. Given that Kss1 is shared by the two pathways, we investigated its role in signal coordination. Thus, we activated both pathways with a combination of salt and pheromone, and in cells lacking the shared MAPK (Kss1) or in cells lacking either of the redundant branches (Sln1 or Sho1). We systematically evaluated the activation of MAPKs using phos-tag western blotting, translocation of Hog1 using fluorescence microscopy, as well as pheromone and salt-induced transcriptional changes using pathway reporters and next generation sequencing. We found that the seemingly redundant HOG components have distinct roles: whereas both Sho1 and Sln1 mediate HOG signaling, Sho1 alone mediates cross talk between the HOG and mating pathways, and does so through Kss1. More broadly, our findings show that redundant components act on shared components to direct concurrent and multiple signals and adapt to sudden environmental changes.