The RGS domain-containing fission yeast protein, Rgs1p, regulates pheromone signalling and is required for mating

Background: When nutritionally starved, the fission yeast Schizosaccharomyc es pombe enters a cell differentiation process which leads to mating and me iosis. The Ste11 protein is a key regulator of this differentiation pathway , activating the transcription of mating and meiotic genes upon starvation. Results: Here, we describe rgs1, a member of the Regulator of G-protein Sig nalling (RGS) family, as a novel Ste11 target gene. rgs1 expression require s both an Ste11-mediated nitrogen starvation signal and the pheromone-induc ed activation of the Byr2/Byr1/Spk1 MAPK pathway. We show that rgs1 deletio n results in a sensitivity to pheromone and in a mating defect. Delta rgs1 cells initiate the mating pathway normally, undergoing sexual agglutination and G1 arrest, while inducing pheromone-dependent transcription, but then fail to fuse with a mating partner while elongating abnormal conjugation tu bes. Endogenous Rgs1 tagged with GFP localizes to the nucleus and cytoplasm , and this localization pattern is not altered during pheromone treatment. Importantly, Rgs1 function requires its C-terminal RGS domain, as well as a central DEP domain and a novel homology domain present in its N-terminal r egion (Fungal-DR domain). Conclusions: These results demonstrate that rgs1 expression requires nutrit ional starvation and pheromone signalling. Rgs1 negatively regulates pherom one signalling during mating, acting in a negative feedback loop that is es sential for the mating process.