Functional Interactions and Evolution of cAMP-PKA Signaling in Saccharomyces

Abstract

In an attempt to gain more insight on functional evolution of cAMP-PKA pathway I have taken a comparative approach and examined functional interactions of cAMP-PKA signaling in well-studied yeast developmental programs and closely related Saccharomyces sensu stricto. species. I have shown that variation in cAMP-PKA signaling contributes significantly to variation in developmental responses in S cerevisiae. Variation in pseudohyphal growth and sporulation, two inversely correlated developmental strategies to nutrient limitation in yeast, proportional to variation in intracellular cAMP levels. S. cerevisiae strains proficient in pseudohyphal growth have higher intracellular cAMP concentrations relative to strains that sporulate efficiently. Phenotypic, genetic and signaling data presented here suggest that the cAMP-PKA signaling underlies a phenotypic trade-off between sporulation and pseudohyphal growth in S. cerevisiae.Further investigation into the role of cAMP-PKA signaling in closely related S paradoxus and S bayanus revealed an antagonistic function of cAMP-PKA signaling for developmental responses in S. bayanus. Unlike in S. cerevisiae, increased cAMP concentrations surprisingly inhibit pseudohyphal response in S. bayanus. Another unanticipated finding in this work is that in S. bayanus. Flo11, required for pseudohyphal differentiation in S. cerevisiae, is dispensable. Additionally, interactions of cAMP-PKA signaling and the general-stress response mechanism appear reversed in S. bayanus. As shown by deletion mutation, gene expression and pharmacological treatment data, altered interactions and alternative targets downstream of cAMP-PKA could critically contribute to alternative regulation of nutrient-induced development in S. bayanus.Intracellular cAMP concentrations show decaying oscillations upon glucose replenishment in derepressed yeast cells. The quantitative characteristics of oscillations are distinct within and between Saccharomyces species. Given the tight regulation of cAMP levels and its critical role, the variation in cAMP oscillatory dynamics could be reflective of differential interactions of cAMP-PKA signaling that also underlie induction of developmental programs to changing environments. As such, intracellular cAMP levels and dynamics could potentially be used as molecular phenotypes.