4.8 Article

Negative feedback that improves information transmission in yeast signalling

Journal

NATURE
Volume 456, Issue 7223, Pages 755-761

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nature07513

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Funding

  1. Alpha Project at the Center for Quantitative Genome Function
  2. NIH Center of Excellence in Genomic Science [P50 HG02370]
  3. National Human Genome Research Institute

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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.

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