Single-cell dynamics and variability of MAPK activity in a yeast differentiation pathway

Area of Science:

• Cell Biology
• Molecular Biology
• Systems Biology

Background:

• Yeast mating involves a MAPK pathway for gene induction, cell-cycle arrest, and polarized growth.
• Previous studies lacked real-time measurements of MAPK activity during yeast mating, limiting understanding of single-cell signaling.

Purpose of the Study:

• To monitor and characterize MAPK (Fus3 and Kss1) activity dynamics in live yeast cells during pheromone response.
• To elucidate the role of MAPK activity in cell-cycle progression, gene expression, and cell fusion during mating.

Main Methods:

• Utilized a yeast-optimized FRET-based mammalian Erk-activity reporter to measure Fus3 and Kss1 activity in real-time.
• Analyzed temporal dynamics, dose dependence, cell cycle influences, and spatial patterns of MAPK activity.

Main Results:

• Mating MAPK activity shows distinct temporal dynamics, rapid reversibility, and graded dose dependence.
• Complex dose response is influenced by cyclin-mediated scaffold phosphorylation and Fus3 autoregulation.
• Cell cycle-dependent patterns and diverse spatial activity emerge, impacting gene expression and cell fusion.

Conclusions:

• Detailed spatiotemporal MAPK activity is crucial for yeast mating and developmental fate.
• MAPK activity dynamics play a key role in successful cell fusion and morphogenic reorganization.
• This work provides a comprehensive view of MAPK signaling in a unicellular differentiation system.