Mating yeast cells concentrate the pheromone receptor and its G protein as polarized crescents at the default polarity site that then track to the eventual chemotropic site

Chemotropism and chemotaxis are fundamental processes required for a broad range of biological phenomena. The mating process of budding yeast ( Saccharomyces cerevisiae ) is, to date, the best‐studied example of chemotropism. In mating mixtures, haploid yeast cells can interpret a shallow pheromone gradient, chemotrope toward the closest mating partner, and fuse to form a diploid zygote. The molecular machinery required for polarized growth has been well characterized. However, how yeast cells accurately position the polarity machinery towards the source of pheromone is unclear. It is well known that the pheromone receptor and its cognate G protein are uniformly distributed on the plasma membrane of vegetative cells, and that they polarize in response to pheromone. In our published model of yeast gradient sensing, inhibition of receptor phosphorylation by Gβg results in differential phosphorylation of the receptor across the cell surface, and consequently, lesser internalization of the receptor and G protein on the up‐gradient side of the cell. A key question is how the uniformly distributed surface receptor competes for a limiting amount of G protein. Here we show that in mating cells, the initially uniform receptor and G protein first localize as polarized crescents at the default polarity site. The receptor and G protein crescents then track along the plasma membrane until they reach the region of highest pheromone concentration, centered around the position at which the cell ultimately shmoos towards its partner. We also show that polarization of Gβ to the default polarity site is independent of receptor phosphorylation and polarization, whereas Gβ tracking from the default site to the eventual chemotropic site does not occur if receptor phosphorylation and redistribution are blocked. These observations suggest a new mechanism that localizes the receptor with its much less abundant G protein. In our revised model, we propose that mating cells that are arrested in G1 concentrate Gβg at the default polarity site, likely through its interaction with Far1‐Bem1‐Cdc24‐Cdc42. The polarized Gβg then protects the receptor from being phosphorylated and internalized, thereby triggering local accumulation of the receptor and G protein. Because the pheromone gradient is mirrored by a gradient of signaling activation within the receptor/G‐protein crescent, there are higher proportions of active‐unphosphorylated receptors and active G protein closer to the pheromone source. The peak of signaling activity incrementally moves up the pheromone gradient, as unprotected receptors are phosphorylated and co‐internalized with G proteins at the back, while vesicles containing nascent receptors and G proteins preferentially dock where the receptor is most abundant. Support or Funding Information NSF