| Title: | Negative feedback that improves information transmission in yeast signalling |
| Author(s): | Yu RC; Pesce CG; Colman-Lerner A; Lok L; Pincus D; Serra E; Holl M; Benjamin K; Gordon A; Brent R; |
| Address: | "Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, California 94704, USA. ryu@molsci.org" |
| ISSN/ISBN: | 1476-4687 (Electronic) 0028-0836 (Print) 0028-0836 (Linking) |
| 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" |
| Keywords: | "Dose-Response Relationship, Drug Feedback, Physiological/*physiology GTPase-Activating Proteins/metabolism Mitogen-Activated Protein Kinases/*metabolism Pheromones/*metabolism/pharmacology Protein Binding Saccharomyces cerevisiae/drug effects/metabolism/*;" |
| Notes: | "MedlineYu, Richard C Pesce, C Gustavo Colman-Lerner, Alejandro Lok, Larry Pincus, David Serra, Eduard Holl, Mark Benjamin, Kirsten Gordon, Andrew Brent, Roger eng P50 HG02370/HG/NHGRI NIH HHS/ R01 GM097479/GM/NIGMS NIH HHS/ P50 HG002370-03/HG/NHGRI NIH HHS/ P50 HG002370-04S1/HG/NHGRI NIH HHS/ P50 HG002370-03S1/HG/NHGRI NIH HHS/ P50 HG002370-02/HG/NHGRI NIH HHS/ P50 HG002370-05/HG/NHGRI NIH HHS/ P50 HG002370/HG/NHGRI NIH HHS/ P50 HG002370-04/HG/NHGRI NIH HHS/ P50 HG002370-05S1/HG/NHGRI NIH HHS/ P50 HG002370-01A1S1/HG/NHGRI NIH HHS/ P50 HG002370-01A1/HG/NHGRI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2008/12/17 Nature. 2008 Dec 11; 456(7223):755-61. doi: 10.1038/nature07513" |
