The signaling mucins Msb2 and Hkr1 differentially regulate the filamentation mitogen-activated protein kinase pathway and contribute to a multimodal response

Abstract

A central question in the area of signal transduction is why pathways utilize common components. In the budding yeast Saccharomyces cerevisiae, the HOG and filamentous growth (FG) MAPK pathways require overlapping components but are thought to be induced by different stimuli and specify distinct outputs. To better understand the regulation of the FG pathway, we examined FG in one of yeast's native environments, the grape-producing plant Vitis vinifera. In this setting, different aspects of FG were induced in a temporal manner coupled to the nutrient cycle, which uncovered a multimodal feature of FG pathway signaling. FG pathway activity was modulated by the HOG pathway, which led to the finding that the signaling mucins Msb2p and Hkr1p, which operate at the head of the HOG pathway, differentially regulate the FG pathway. The two mucins exhibited different expression and secretion patterns, and their overproduction induced nonoverlapping sets of target genes. Moreover, Msb2p had a function in cell polarization through the adaptor protein Sho1p that Hkr1p did not. Differential MAPK activation by signaling mucins brings to light a new point of discrimination between MAPK pathways.