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Protected pheromone receptors signal
In budding yeast, opposite mating types signal to each other by secreting distinct pheromones, which bind to and activate receptors on the surface of compatible cells. The stimulated cell produces a mating projection (shmoo), which is enriched in pheromone receptors, that grows along the pheromone gradient to fuse with the shmoo of a mating partner. Ismael et al. imaged pheromone-treated yeast cells and found that the G protein β subunit, which is activated by ligand-bound pheromone receptors, competed with a kinase for access to receptors at the site closest to the highest amount of pheromone. In this way, the phosphorylation and internalization of receptors occurring in the rest of the cell was inhibited at this local site, which enabled the receptor to persist at the cell surface and stimulate growth of the shmoo.
Gradient-directed cell migration (chemotaxis) and growth (chemotropism) are processes that are essential to the development and life cycles of all species. Cells use surface receptors to sense the shallow chemical gradients that elicit chemotaxis and chemotropism. Slight asymmetries in receptor activation are amplified by downstream signaling systems, which ultimately induce dynamic reorganization of the cytoskeleton. During the mating response of budding yeast, a model chemotropic system, the pheromone receptors on the plasma membrane polarize to the side of the cell closest to the stimulus. Although receptor polarization occurs before and independently of actin cable–dependent delivery of vesicles to the plasma membrane (directed secretion), it requires receptor internalization. Phosphorylation of pheromone receptors by yeast casein kinase 1 or 2 (Yck1/2) stimulates their internalization. We showed that the pheromone-responsive Gβγ dimer promotes the polarization of the pheromone receptor by interacting with Yck1/2 and locally inhibiting receptor phosphorylation. We also found that receptor phosphorylation is essential for chemotropism, independently of its role in inducing receptor internalization. A mathematical model supports the idea that the interaction between Gβγ and Yck1/2 results in differential phosphorylation and internalization of the pheromone receptor and accounts for its polarization before the initiation of directed secretion.