PLOS Biol. https://doi.org/10.1371/journal.pbio.3000484 (2019)
Sensing of chemical gradients is important for cells to orient their growth and migration. In the yeast Saccharomyces cerevisiae, cells of opposite mating types secrete pheromones that act on their partners through a G-protein-coupled receptor (GPCR) in both cell types. GPCR activation leads to transcription of mating-related genes and concentration of the small G protein Cdc42, a regulator of cell polarity, to a distinct site on the cell cortex to orient the cytoskeleton. To understand how yeast cells sense the pheromone gradient to direct polarization, Henderson et al. performed various imaging and modeling studies, revealing a spatial mechanism that senses the ratio of occupied versus unoccupied receptors, amplifying the pheromone gradient. An exploratory mechanism then samples ligand concentrations across the cell during an indecisive phase, in which the polarity site wanders around the cortex, and is followed by a committed phase, in which cells are prepared for mating. These mechanisms act to align the Cdc42 polarity site and improve the search for a mating partner even in situations of non-uniform GPCR distribution.