dose-to-duration encoding and signaling beyond saturation in intracellular signaling networksdose-to-duration编码和信号超出饱和在胞内信号网络.pdfVIP

Dose-to-Duration Encoding and Signaling beyond Saturation in Intracellular Signaling Networks 1,2 3 3,4 3 Marcelo Behar , Nan Hao , Henrik G. Dohlman , Timothy C. Elston * 1 Department of Physics, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, United States of America, 2 Program in Cellular and Molecular Biophysics, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, United States of America, 3 Department of Pharmacology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, United States of America, 4 Department of Biochemistry and Biophysics, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, United States of America Abstract The cellular response elicited by an environmental cue typically varies with the strength of the stimulus. For example, in the yeast Saccharomyces cerevisiae, the concentration of mating pheromone determines whether cells undergo vegetative growth, chemotropic growth, or mating. This implies that the signaling pathways responsible for detecting the stimulus and initiating a response must transmit quantitative information about the intensity of the signal. Our previous experimental results suggest that yeast encode pheromone concentration as the duration of the transmitted signal. Here we use mathematical modeling to analyze possible biochemical mechanisms for performing this ‘‘dose-to-duration’’ conversion. We demonstrate that modulation of signal duration increases the range of stimulus concentrations for which dose-dependent responses are possible; this increased dynamic range produces the counterintuitive result of ‘‘signaling beyond saturation’’ in which dose-dependent responses are still possible after apparent saturation of the