title: Negative feedback that improves information transmission in yeast signalling.
abstract: Haploid Saccharomyces cerevisiae yeast cells use a prototypic cell signalling system to transmit information about the extracellular concentration of mating pheromone secreted by potential mating partners. The ability of cells to respond distinguishably to different pheromone concentrations depends on how much information about pheromone concentration the system can transmit. Here we show that the mitogen-activated protein kinase Fus3 mediates fast-acting negative feedback that adjusts the dose response of the downstream system response to match the dose response of receptor-ligand binding. This 'dose-response alignment', defined by a linear relationship between receptor occupancy and downstream response, can improve the fidelity of information transmission by making downstream responses corresponding to different receptor occupancies more distinguishable and reducing amplification of stochastic noise during signal transmission. We also show that one target of the feedback is a previously uncharacterized signal-promoting function of the regulator of G-protein signalling protein Sst2. Our work suggests that negative feedback is a general mechanism used in signalling systems to align dose responses and thereby increase the fidelity of information transmission.
authors.affiliation: Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, California 94704, USA. ryu@molsci.org
authors.forename: Richard C
authors.initials: RC
authors.lastname: Yu
authors.forename: C Gustavo
authors.initials: CG
authors.lastname: Pesce
authors.forename: Alejandro
authors.initials: A
authors.lastname: Colman-Lerner
authors.forename: Larry
authors.initials: L
authors.lastname: Lok
authors.forename: David
authors.initials: D
authors.lastname: Pincus
authors.forename: Eduard
authors.initials: E
authors.lastname: Serra
authors.forename: Mark
authors.initials: M
authors.lastname: Holl
authors.forename: Kirsten
authors.initials: K
authors.lastname: Benjamin
authors.forename: Andrew
authors.initials: A
authors.lastname: Gordon
authors.forename: Roger
authors.initials: R
authors.lastname: Brent
mesh_terms: D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010675:Pheromones / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020710:RGS Proteins
chemical_list: D020690:GTPase-Activating Proteins; D020928:Mitogen-Activated Protein Kinases; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; C094301:SST2 protein, S cerevisiae; D020710:RGS Proteins; C075580:FUS3 protein, S cerevisiae