Ecological inducers of the yeast filamentousgrowth pathway reveal environment-dependent roles for pathway components

Signaling modules, such as mitogen-activated protein kinase (MAPK) pathways, are evolutionarily conserved drivers of cell differentiationand stress responses. In many fungal species including pathogens, MAPK pathways control filamentousgrowth, where cells differentiateinto an elongated cell type. The convenient model budding yeast Saccharomyces cerevisiae undergoes filamentousgrowth by the filamentousgrowth (fMAPK) pathway; however, the inducers of the pathway remain unclear, perhaps because pathway activity has been mainly studied in laboratory conditions. To address this knowledge gap, an ecological framework was used, which uncovered new fMAPK pathway inducers, including pectin, a material found in plants, and the metabolic byproduct ethanol. We also show that induction by a known inducer of the pathway, the non-preferred carbon source galactose, required galactose metabolism and induced the pathway differentlythan glucose limitation or other non-preferred carbon sources. By exploring fMAPK pathway function in fruit, we found that induction of the pathway led to visible digestion of fruit rind through a known target, PGU1, which encodes a pectolytic enzyme. Combinations of inducers (galactose and ethanol) stimulated the pathway to near-maximal levels, which showed dispensability of several fMAPK pathway components (e.g., mucin sensor, p21-activated kinase), but not others (e.g., adaptor, MAPKKK) and required the Ras2-protein kinase A pathway. This included a differencebetween the transcription factor binding partners for the pathway, as Tec1p, but not Ste12p, was partly dispensable for fMAPK pathway activity. Thus, by exploring ecologically relevant stimuli, new modes of MAPK pathway signaling were uncovered, perhaps revealing how a pathway can respond differentlyto specificenvironments.