Negative feedback that improves information transmission in yeast signalling

Richard C. Yu (), C. Gustavo Pesce, Alejandro Colman-Lerner, Larry Lok, David Pincus, Eduard Serra, Mark Holl, Kirsten Benjamin, Andrew Gordon and Roger Brent ()
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Richard C. Yu: Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, California 94704, USA
C. Gustavo Pesce: Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, California 94704, USA
Alejandro Colman-Lerner: Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, California 94704, USA
Larry Lok: Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, California 94704, USA
David Pincus: Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, California 94704, USA
Eduard Serra: Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, California 94704, USA
Mark Holl: Microscale Life Sciences Center, University of Washington, Seattle, Washington 98195, USA
Kirsten Benjamin: Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, California 94704, USA
Andrew Gordon: Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, California 94704, USA
Roger Brent: Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, California 94704, USA

Nature, 2008, vol. 456, issue 7223, 755-761

Abstract: 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.

Date: 2008
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DOI: 10.1038/nature07513

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