KIS,aKinaseAssociatedwithMicrotubuleRegulators, EnhancesTranslationofAMPAReceptorsandStimulates DendriticSpineRemodeling

摘要: Local regulation of protein synthesis allows a neuron to rapidly alter the proteome in response synaptic signals, an essential mechanism plasticity that is altered many neurological diseases. Synthesis proteins under local control and muchofthisregulationoccursthroughstructurestermedRNAgranules.KISisaproteinkinasethatassociateswithstathmin,amodulatorofthetubulincytoskeleton.Furthermore,KISisfoundinRNAgranulesandstimulatestranslationdrivenbythe-actin3UTRin neurites.HereweexplorethephysiologicalandmolecularmechanismsunderlyingtheactionofKISonhippocampalsynapticplasticity mice. KIS downregulation compromises spine development, alters actin dynamics, reduces postsynaptic responsiveness. The absenceofKISresultsinasignificantdecreaseofproteinlevelsofPSD-95,apostsynapticscaffoldingprotein,andtheAMPARsubunits GluR1andGluR2inaCPEB3-dependentmanner.Underlyingitsroleinspinematuration,KISisabletosuppressthespinedevelopmental defects caused by CPEB3 overexpression. Moreover, either direct or indirect mechanisms, counteracts inhibitory activity CPEB3ontheGluR23UTRatbothmRNAtranslationandpolyadenylationlevels.Ourstudyprovidesinsightsintothemechanismsthat mediatedendriticspinemorphogenesisandfunctionalsynapticmaturation,andsuggestsKISasalinkregulatingspinecytoskeletonand postsynapticactivityinmemoryformation.