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

Ignacio Garcia (1) , Sara Orellana-Muñoz (1) , Lucía Ramos-Alonso (1) , Aram N Andersen (1) , Christine Zimmermann (2) , Jens Eriksson (3) , Stig Ove Bøe (1) , Petra Kaferle (4) , Manolis Papamichos-Chronakis (5) , Pierre Chymkowitch (1) , Jorrit M Enserink (1)

1 UiO - University of Oslo
2 University Medical Center of the Johannes Gutenberg-University Mainz
3 Uppsala University
4 Dynamique du noyau [Institut Curie]
5 University of Liverpool

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.

Mots clés: Kel1; MAPK signaling; Ste5; noise suppression; pheromone signaling pathway

Domaines: Sciences du Vivant [q-bio]

Ignacio Garcia, Sara Orellana-Muñoz, Lucía Ramos-Alonso, Aram N Andersen, Christine Zimmermann, et al.. Kel1 is a phosphorylation-regulated noise suppressor of the pheromone signaling pathway. Cell Reports, 2021, 37 (13), pp.110186. ⟨10.1016/j.celrep.2021.110186⟩. ⟨hal-03531131⟩