Particle-based simulations reveal two positive feedback loops allow relocation and stabilization of the polarity site during yeast mating

PLoS Comput Biol. 2023 Oct 2;19(10):e1011523. doi: 10.1371/journal.pcbi.1011523. eCollection 2023 Oct.

Abstract

Many cells adjust the direction of polarized growth or migration in response to external directional cues. The yeast Saccharomyces cerevisiae orient their cell fronts (also called polarity sites) up pheromone gradients in the course of mating. However, the initial polarity site is often not oriented towards the eventual mating partner, and cells relocate the polarity site in an indecisive manner before developing a stable orientation. During this reorientation phase, the polarity site displays erratic assembly-disassembly behavior and moves around the cell cortex. The mechanisms underlying this dynamic behavior remain poorly understood. Particle-based simulations of the core polarity circuit revealed that molecular-level fluctuations are unlikely to overcome the strong positive feedback required for polarization and generate relocating polarity sites. Surprisingly, inclusion of a second pathway that promotes polarity site orientation generated relocating polarity sites with properties similar to those observed experimentally. This pathway forms a second positive feedback loop involving the recruitment of receptors to the cell membrane and couples polarity establishment to gradient sensing. This second positive feedback loop also allows cells to stabilize their polarity site once the site is aligned with the pheromone gradient.

MeSH terms

  • Cell Communication
  • Cell Polarity / physiology
  • Feedback
  • Pheromones / metabolism
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Pheromones