dyschronic, a Drosophila Homolog of a Deaf-Blindness Gene, Regulates Circadian Output and Slowpoke Channels 英文参考文献.docVIP
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dyschronic, a Drosophila Homolog of a Deaf-Blindness Gene, Regulates Circadian Output and Slowpoke Channels 英文参考文献
dyschronic,aDrosophilaHomologofaDeaf-Blindness
Gene,RegulatesCircadianOutputandSlowpoke
Channels
JamesE.C.Jepson,MohammadShahidullah.,AngeliqueLamaze.,DrewPeterson,HuihuiPan,
KyungheeKoh*
DepartmentofNeuroscience,FarberInstituteofNeuroscience,KimmelCancerCenter,ThomasJeffersonUniversity,Philadelphia,Pennsylvania,UnitedStatesofAmerica
Abstract
Many aspects of behavior and physiology are under circadian control. In Drosophila, the molecular clock that regulates
rhythmicpatternsofbehaviorhasbeenextensivelycharacterized.Incontrast,geneticlociinvolvedinlinkingtheclockto
alterationsinmotoractivityhaveremainedelusive.Inaforward-geneticscreen,weuncoveredanewcomponentofthe
circadianoutputpathway,whichwehavetermeddyschronic(dysc).dyscmutantsexhibitarrhythmiclocomotorbehavior,
yettheireclosionrhythmsarenormalandclockproteincyclingremainsintact.Intriguingly,dyscistheclosestDrosophila
homologofwhirlin,agenelinkedtotypeIIUshersyndrome,theleadingcauseofdeaf-blindnessinhumans.Whirlinand
otherUsherproteinsareexpressedinthemammaliancentralnervoussystem,yettheirfunctionintheCNShasnotbeen
investigated.WeshowthatDYSCisexpressedinmajorneuronaltractsandregulatesexpressionofthecalcium-activated
potassiumchannelSLOWPOKE(SLO),anionchannelalsorequiredinthecircadianoutputpathway.SLOandDYSCareco-
localized in the brain and control each other’s expression post-transcriptionally. Co-immunoprecipitation experiments
demonstratetheyformacomplex,suggestingtheyregulateeachotherthroughprotein–proteininteraction.Furthermore,
electrophysiologicalrecordingsofneuronsintheadultbrainshowthatSLO-dependentcurrentsaregreatlyreducedindysc
mutants.OurworkidentifiesaDrosophilahomologofadeaf-blindnessgeneasanewcomponentofthecircadianoutput
pathway and an important regulator of ion channel expression, and suggests novel roles for Usher proteins in the
mammaliannervoussystem.
Citation:JepsonJEC,ShahidullahM,LamazeA,PetersonD,PanH,etal.(2012)dyschronic,aDrosophilaHomologofaDeaf-BlindnessGene,RegulatesCircadian
Outpu
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