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

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

doi:10.1016/j.celrep.2021.110186

Abstract

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.

Highlights

A crucial aspect of any organism’s well-being is the ability of cells to respond to changes in their internal and external milieu
Intrinsic noise is caused by inherent stochastic events in biochemical processes that can occur at various levels during gene expression, such as transcriptional initiation, mRNA degradation, translational initiation, and protein degradation, as well as during signal transduction (Raser and O’Shea, 2005)
Extrinsic noise is caused by differences among cells, in either their local environment or the concentration or activity of any factor that influences gene expression (Raser and O’Shea, 2005; Volfson et al, 2006), such as age, cell cycle stage, metabolic state, and the number and quality of proteins and organelles distributed to the mother and daughter cell during cell division

Summary

Introduction

A crucial aspect of any organism’s well-being is the ability of cells to respond to changes in their internal and external milieu. Noise has been best studied at the level of gene expression, where it is often referred to as the stochastic variation in the protein expression level of a gene among isogenic cells in a homogenous environment (Raser and O’Shea, 2005; Wang and Zhang, 2011). Gene expression noise can arise from intrinsic and extrinsic variations (Raser and O’Shea, 2005). Intrinsic noise is caused by inherent stochastic events in biochemical processes that can occur at various levels during gene expression, such as transcriptional initiation, mRNA degradation, translational initiation, and protein degradation, as well as during signal transduction (Raser and O’Shea, 2005). Extrinsic noise is caused by differences among cells, in either their local environment or the concentration or activity of any factor that influences gene expression (Raser and O’Shea, 2005; Volfson et al, 2006), such as age, cell cycle stage, metabolic state, and the number and quality of proteins and organelles distributed to the mother and daughter cell during cell division

Methods

Results

Discussion

Conclusion