Dose-to-Duration Encoding and Signaling beyond Saturation in Intracellular Signaling Networks 英文参考文献.docVIP

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Dose-to-Duration Encoding and Signaling beyond Saturation in Intracellular Signaling Networks 英文参考文献.doc

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Dose-to-Duration Encoding and Signaling beyond Saturation in Intracellular Signaling Networks 英文参考文献

Dose-to-DurationEncodingandSignalingbeyond SaturationinIntracellularSignalingNetworks MarceloBehar1,2,NanHao3,HenrikG.Dohlman3,4,TimothyC.Elston3* 1DepartmentofPhysics,UniversityofNorthCarolinaChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica,2PrograminCellularandMolecularBiophysics, UniversityofNorthCarolinaChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica,3DepartmentofPharmacology,UniversityofNorthCarolinaChapelHill, ChapelHill,NorthCarolina,UnitedStatesofAmerica,4DepartmentofBiochemistryandBiophysics,UniversityofNorthCarolinaChapelHill,ChapelHill,NorthCarolina, UnitedStatesofAmerica Abstract Thecellularresponseelicitedbyanenvironmentalcuetypicallyvarieswiththestrengthofthestimulus.Forexample,inthe yeast Saccharomyces cerevisiae, the concentration of mating pheromone determines whether cells undergo vegetative growth,chemotropicgrowth,ormating.Thisimpliesthatthesignalingpathwaysresponsiblefordetectingthestimulusand initiatingaresponsemusttransmitquantitativeinformationabouttheintensityofthesignal.Ourpreviousexperimental results suggest that yeast encode pheromone concentration as the duration of the transmitted signal. Here we use mathematicalmodelingtoanalyzepossiblebiochemicalmechanismsforperformingthis‘‘dose-to-duration’’conversion.We demonstratethatmodulationofsignaldurationincreasestherangeofstimulusconcentrationsforwhichdose-dependent responsesarepossible;thisincreaseddynamicrangeproducesthecounterintuitiveresultof‘‘signalingbeyondsaturation’’ inwhichdose-dependentresponsesarestillpossibleafterapparentsaturationofthereceptors.Weproposeamechanism fordose-to-durationencodingintheyeastpheromonepathwaythatisconsistentwithcurrentexperimentalobservations. Most previous investigations of information processing by signaling pathways have focused on amplitude encoding without considering temporal aspects of signal transduction. Here we demonstrate that dose-to-duration encoding provides cells with an alternative mechanism for processing and transmit