title: MAPK-mediated bimodal gene expression and adaptive gradient sensing in yeast.
abstract: The mating pathway in Saccharomyces cerevisiae has been the focus of considerable research effort, yet many quantitative aspects of its regulation still remain unknown. Using an integrated approach involving experiments in microfluidic chips and computational modelling, we studied gene expression and phenotypic changes associated with the mating response under well-defined pheromone gradients. Here we report a combination of switch-like and graded pathway responses leading to stochastic phenotype determination in a specific range of pheromone concentrations. Furthermore, we show that these responses are critically dependent on mitogen-activated protein kinase (MAPK)-mediated regulation of the activity of the pheromone-response-specific transcription factor, Ste12, as well as on the autoregulatory feedback of Ste12. In particular, both the switch-like characteristics and sensitivity of gene expression in shmooing cells to pheromone concentration were significantly diminished in cells lacking Kss1, one of the MAP kinases activated in the mating pathway. In addition, the dynamic range of gradient sensing of Kss1-deficient cells was reduced compared with wild type. We thus provide unsuspected functional significance for this kinase in regulation of the mating response.
authors.affiliation: Department of Biomedical Engineering and Whitaker Institute of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Paliwal
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Iglesias
authors.forename: Kyle
authors.initials: K
authors.lastname: Campbell
authors.forename: Zoe
authors.initials: Z
authors.lastname: Hilioti
authors.forename: Alex
authors.initials: A
authors.lastname: Groisman
authors.forename: Andre
authors.initials: A
authors.lastname: Levchenko
mesh_terms: D000220:Adaptation, Biological / Q000187:drug effects / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D044085:Microfluidics; D020928:Mitogen-Activated Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010675:Pheromones / Q000378:metabolism / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D010675:Pheromones; C489241:STE12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C075580:FUS3 protein, S cerevisiae; C541984:KSS1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases