Gβ promotes pheromone receptor polarization and yeast chemotropism by inhibiting receptor phosphorylation.

Gradient-directed cell migration and growth are universal processes, 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 spatial cues are amplified by downstream signaling systems, which ultimately induce polarization of the cytoskeleton. During the mating response of budding yeast, a model chemotropic system, the pheromone receptor polarizes to the up-gradient side of the cell, but how this happens is unknown. Although receptor polarization occurs prior to and independently of directed secretion, it requires receptor internalization. Casein kinase (Yck1/2)-dependent receptor phosphorylation triggers receptor internalization. Here we show that the pheromone-responsive Gβγ promotes polarization of its receptor by interacting with Yck1/2 and locally inhibiting receptor phosphorylation. We also present evidence that implicates receptor phosphorylation in chemotropism, independent of its role as a trigger for receptor internalization. A mathematical model supports the idea that Gβγ-Yck1/2 interaction results in differential phosphorylation and internalization of the receptor and accounts for its polarization upstream of directed secretion.