Robust Spatial Sensing of Mating Pheromone Gradients by Yeast Cells 英文参考文献.docVIP

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Robust Spatial Sensing of Mating Pheromone Gradients by Yeast Cells 英文参考文献.doc

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Robust Spatial Sensing of Mating Pheromone Gradients by Yeast Cells 英文参考文献

RobustSpatialSensingofMatingPheromoneGradients byYeastCells TravisI.Moore1,2,Ching-ShanChou2,3,QingNie2,3,NooLiJeon2,4,Tau-MuYi1,2 * 1Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, United States of America, 2Center for Complex Biological Systems, UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica,3DepartmentofMathematics,UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesof America,4DepartmentofBiomedicalEngineering,UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica Abstract Projectingormovingupachemicalgradientisauniversalbehavioroflivingorganisms.WetestedtheabilityofS.cerevisiae a-cellstosenseandrespondtospatialgradientsofthematingpheromonea-factorproducedinamicrofluidicschamber; thefocuswasonbar1Dstrains,whichdonotdegradethepheromoneinput.Theyeastcellsexhibitedgoodaccuracywith thematingprojectiontypicallypointinginthecorrectdirectionupthegradient(,80%undercertainconditions),excellent sensitivitytoshallowgradients,andbroaddynamicrangesothatgradient-sensingwasrelativelyrobustovera1000-fold rangeofaveragea-factorconcentrations.Optimaldirectionalsensingoccurredatlowerconcentrations(5nM)closetothe Kdofthereceptorandwithsteepergradientslopes.Pheromonesupersensitivemutations(sst2Dandste2300D)thatdisrupt thedown-regulationofheterotrimericG-proteinsignalingcauseddefectsinbothsensingandresponse.Interestingly,yeast cells employed adaptive mechanisms to increase the robustness of the process including filamentous growth (i.e. directionaldistalbudding)upthegradientatlowpheromoneconcentrations,bendingoftheprojectiontobemorealigned withthegradient,andformingamoreaccuratesecondprojectionwhenthefirstprojectionwasinthewrongdirection. Finally,thecellswereabletoamplifyashallowexternalgradientsignalofa-factortoproduceadramaticpolarizationof signalingproteinsatthefrontofthecell.Mathematicalmodelingrevealedinsightsintothemechanismofthisamplification andhowthesupersensitivemutantscandisrupt