MAPK-mediated bimodal gene expression and adaptive gradient sensing in yeast.

Area of Science:

• Cellular Biology
• Systems Biology
• Genetics

Background:

• The mating pathway in Saccharomyces cerevisiae is complex, with many quantitative regulatory aspects yet to be fully understood.
• Understanding gene expression and phenotypic changes under controlled conditions is crucial for elucidating pathway dynamics.

Purpose of the Study:

• To investigate quantitative aspects of the Saccharomyces cerevisiae mating pathway regulation.
• To analyze gene expression and phenotypic changes in response to defined pheromone gradients.
• To elucidate the role of mitogen-activated protein kinase (MAPK) signaling and transcription factor Ste12 in mating pathway regulation.

Main Methods:

• Integrated approach combining microfluidic chip experiments and computational modeling.
• Studied gene expression and phenotypic changes under well-defined pheromone gradients.
• Utilized genetic analysis, including Kss1-deficient mutants, to assess kinase function.

Main Results:

• Observed a combination of switch-like and graded pathway responses, leading to stochastic phenotype determination within specific pheromone concentration ranges.
• Demonstrated critical dependence on MAPK-mediated regulation of Ste12 activity and Ste12 autoregulatory feedback.
• Found that Kss1 deficiency significantly diminished switch-like characteristics, gene expression sensitivity, and the dynamic range of gradient sensing.

Conclusions:

• The yeast mating response exhibits complex regulatory dynamics involving both switch-like and graded responses.
• Mitogen-activated protein kinase (MAPK) signaling, particularly through Kss1, plays a critical, previously unsuspected role in regulating Ste12 activity and pheromone response sensitivity.
• Kss1 is essential for sensitive gradient sensing and robust gene expression regulation during the mating process in Saccharomyces cerevisiae.