Translational control as a novel regulator of gradient sensing and chemotropism in yeast

Abstract

The yeast mating pathway regulates haploid cell fusion to form diploids in response to pheromone signaling. Study of this pathway has led to important insights into the structure and function of mitogen-activated protein kinase (MAPK) cascades, yet our understanding of how external signals are converted into specific changes in gene expression and cell morphology is incomplete. For example, the regulators of directional growth (chemotropism) remain poorly defined. Upon pheromone exposure, yeast grow asymmetrically towards a nearby mating partner (chemotropic morphogenesis) and form a mating projection (shmoo). Using non-biased genome-wide screening, we identify >20 novel positive and negative regulators of pheromone gradient sensing, shmoo development, and mating. In addition to known regulators of exocytic and endocytic pathways, several are directly involved in translational control downstream of the G-protein-regulated pheromone and filamentous growth MAPK pathways. These include the Scp160 RNA-binding protein and ribosomal proteins Asc1, Rpl12b and Rpl19b. Importantly, pheromone treatment and Gα (Gpa1) activation both stimulate Scp160 binding to, and inhibition of, Asc1, which acts downstream of glucose-activated Gα (Gpa2) on the filamentous growth pathway. We also identify Rpl12b and Rpl19b as paralog-specific positive regulators of translation of specific mating pathway components, including Scp160. Thus, the different MAPK pathways converge at the level of translational control to regulate signaling.