dTip60 HAT Activity Controls Synaptic Bouton Expansion at the Drosophila Neuromuscular Junction 英文参考文献.docVIP
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dTip60 HAT Activity Controls Synaptic Bouton Expansion at the Drosophila Neuromuscular Junction 英文参考文献
dTip60HATActivityControlsSynapticBoutonExpansion
attheDrosophilaNeuromuscularJunction
JessicaSarthi,FeliceElefant*
DepartmentofBiology,DrexelUniversity,Philadelphia,Pennsylvania,UnitedStatesofAmerica
Abstract
Background: Histone acetylation of chromatin plays a key role in promoting the dynamic transcriptional responses in
neuronsthatinfluencetheneuroplasticitylinkedtocognitiveability,yetthespecifichistoneacetyltransferases(HATs)that
createsuchepigeneticmarksremaintobeelucidated.
MethodsandFindings:HereweusetheDrosophilaneuromuscularjunction(NMJ)asawell-characterizedsynapsemodelto
identifyHATsthatcontrolsynapticremodelingandstructure.WeshowthattheHATdTip60isconcentratedbothpreand
post-synaptically within the NMJ. Presynaptic targeted reduction of dTip60 HAT activity causes a significant increase in
synapticboutonnumberthatspecificallyaffectstypeIsboutons.Theexcessboutonsshowasuppressionoftheactivezone
synapticfunctionmarkerbruchpilot,suggestingdefectsinneurotransmissionfunction.Analysisofmicrotubuleorganization
withintheseexcessboutonsusingimmunohistochemicalstainingtothemicrotubuleassociatedproteinfutschrevealsa
significantincreaseintherearrangementofmicrotubulelooparchitecturethatisrequiredforboutondivision.Moreover,a-
tubulinacetylationlevelsofmicrotubulesspecificallyextendingintotheterminalsynapticboutonsarereducedinresponse
todTip60HATreduction.
Conclusions:OurresultsarethefirsttodemonstrateacausativerolefortheHATdTip60inthecontrolofsynapticplasticity
thatisachieved,atleastinpart,viaregulationofthesynapticmicrotubulecytoskeleton.Thesefindingshaveimplications
fordTip60HATdependantepigeneticmechanismsunderlyingcognitivefunction.
Citation:SarthiJ,ElefantF(2011)dTip60HATActivityControlsSynapticBoutonExpansionattheDrosophilaNeuromuscularJunction.PLoSONE6(10):e26202.
doi:10.1371/journal.pone.0026202
Editor:Mohamed-AliHakimi,FrenchNationalCentreforScientificResearch,France
ReceivedJuly13,2011;AcceptedSeptember22,2011;PublishedOctober27,2011
Copyright: ? 2011 Sarthi,
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