Asymmetric PTEN Distribution Regulated by Spatial Heterogeneity in Membrane-Binding State Transitions.docVIP

AsymmetricPTENDistributionRegulatedbySpatial HeterogeneityinMembrane-BindingStateTransitions SatomiMatsuoka1,2,3,TatsuoShibata3,4,MasahiroUeda1,2,3,5 * 1LaboratoryforCellSignalingDynamics,RIKENQuantitativeBiologyCenter,Suita,Japan,2LaboratoriesforNanobiology,GraduateSchoolofFrontierBiosciences,Osaka University,Suita,Japan,3CREST,JapanScienceandTechnologyAgency(JST),Suita,Japan,4LaboratoriesforPhysicalBiology,RIKENCenterforDevelopmentalBiology, Kobe,Japan,5LaboratoryofSingleMoleculeBiology,DepartmentofBiologicalSciences,GraduateSchoolofScience,OsakaUniversity,Toyonaka,Japan Abstract The molecular mechanisms that underlie asymmetric PTEN distribution at the posterior of polarized motile cells and regulate anterior pseudopod formation were addressed by novel single-molecule tracking analysis. Heterogeneity in the lateralmobilityofPTENonamembraneindicatedtheexistenceofthreemembrane-bindingstateswithdifferentdiffusion coefficientsandmembrane-bindinglifetimes.ThestochasticstatetransitionkineticsofPTENamongthesethreestateswere suggestedtoberegulatedspatiallyalongthecellpolaritysuchthatonlythestablebindingstateisselectivelysuppressedat theanteriormembranetocauselocalPTENdepletion.Byincorporatingexperimentallyobservedkineticparametersintoa simplemathematicalmodel,theasymmetricPTENdistributioncanbeexplainedquantitativelytoillustratetheregulatory mechanisms for cellular asymmetry based on an essential causal link between individual stochastic reactions and stable localizationsoftheensemble. Citation:MatsuokaS,ShibataT,UedaM(2013)AsymmetricPTENDistributionRegulatedbySpatialHeterogeneityinMembrane-BindingStateTransitions.PLoS ComputBiol9(1):e1002862.doi:10.1371/journal.pcbi.1002862 Editor:MarkS.Alber,UniversityofNotreDame,UnitedStatesofAmerica ReceivedMay23,2012;AcceptedNovember10,2012;PublishedJanuary10,2013 Copyright: ? 2013 Matsuoka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,di