Phosphorylation of RGS regulates MAP kinase localization and promotes completion of cytokinesis

• Published in: Life science alliance 2022-10, Vol.5 (10), p.e202101245
• Main Authors: Simke, William C, Johnson, Cory P, Hart, Andrew J, Mayhue, Sari, Craig, P Lucas, Sojka, Savannah, Kelley, Joshua B
• Format: Article
• Language: English
• ISSN: 2575-1077; 2575-1077
• DOI: 10.26508/lsa.202101245

Yeast use the G-protein–coupled receptor signaling pathway to detect and track the mating pheromone. The G-protein–coupled receptor pathway is inhibited by the regulator of G-protein signaling (RGS) Sst2 which induces Gα GTPase activity and inactivation of downstream signaling. G-protein signaling activates the MAPK Fus3, which phosphorylates the RGS; however, the role of this modification is unknown. We found that pheromone-induced RGS phosphorylation peaks early; the phospho-state of RGS controls its localization and influences MAPK spatial distribution. Surprisingly, phosphorylation of the RGS promotes completion of cytokinesis before pheromone-induced growth. Completion of cytokinesis in the presence of pheromone is promoted by the kelch-repeat protein, Kel1 and antagonized by the formin Bni1. We found that RGS complexes with Kel1 and prefers the unphosphorylatable RGS mutant. We also found overexpression of unphosphorylatable RGS exacerbates cytokinetic defects, whereas they are rescued by overexpression of Kel1. These data lead us to a model where Kel1 promotes completion of cytokinesis before pheromone-induced polarity but is inhibited by unphosphorylated RGS binding.