Kel1 is a phosphorylation-regulated noise suppressor of the pheromone signaling pathway

• Published in: Cell reports (Cambridge) Vol. 37; no. 13; p. 110186
• Main Authors: Garcia, Ignacio, Orellana-Muñoz, Sara, Ramos-Alonso, Lucía, Andersen, Aram N., Zimmermann, Christine, Eriksson, Jens, Bøe, Stig Ove, Kaferle, Petra, Papamichos-Chronakis, Manolis, Chymkowitch, Pierre, Enserink, Jorrit M.
• Format: Journal Article
• Language: English; Norwegian
• Published: United States Elsevier Inc 28.12.2021; Cell Press
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Cyclin-Dependent Kinase Inhibitor Proteins - genetics; Cyclin-Dependent Kinase Inhibitor Proteins - metabolism; Kel1; Life Sciences; MAPK signaling; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Noise; noise suppression; pheromone signaling pathway; Pheromones - metabolism; Phosphorylation; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Signal Transduction; Ste5; noise suppression; Kel1; Ste5; pheromone signaling pathway; MAPK signaling
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.110186

Mechanisms have evolved that allow cells to detect signals and generate an appropriate response. The accuracy of these responses relies on the ability of cells to discriminate between signal and noise. How cells filter noise in signaling pathways is not well understood. Here, we analyze noise suppression in the yeast pheromone signaling pathway and show that the poorly characterized protein Kel1 serves as a major noise suppressor and prevents cell death. At the molecular level, Kel1 prevents spontaneous activation of the pheromone response by inhibiting membrane recruitment of Ste5 and Far1. Only a hypophosphorylated form of Kel1 suppresses signaling, reduces noise, and prevents pheromone-associated cell death, and our data indicate that the MAPK Fus3 contributes to Kel1 phosphorylation. Taken together, Kel1 serves as a phospho-regulated suppressor of the pheromone pathway to reduce noise, inhibit spontaneous activation of the pathway, regulate mating efficiency, and prevent pheromone-associated cell death. [Display omitted] •It is not well understood how organisms suppress noise in signaling systems•Kel1 is a noise suppressor of the pheromone pathway in yeast•Spontaneous signaling and pheromone-associated cell death are inhibited by Kel1•Kel1 is regulated by phosphorylation; hyperphosphorylated Kel1 suppresses signaling Unscheduled activation of signaling pathways, such as the pheromone pathway in budding yeast, is associated with fitness cost, and mechanisms have evolved that suppress noise. Garcia et al. describe a noise suppressor of the yeast pheromone pathway, Kel1, which promotes fitness by preventing cell death when the cell encounters pheromone.