A Conserved Function of C. elegans CASY-1 Calsyntenin in Associative Learning 英文参考文献.docVIP

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A Conserved Function of C. elegans CASY-1 Calsyntenin in Associative Learning 英文参考文献.doc

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A Conserved Function of C. elegans CASY-1 Calsyntenin in Associative Learning 英文参考文献

AConservedFunctionofC.elegansCASY-1Calsyntenin inAssociativeLearning Fre′de′ricJ.Hoerndli1,2¤,MichaelWalser1,ErikaFro¨hliHoier1,DominiquedeQuervain4,5 ,Andreas Papassotiropoulos2,3,AlexHajnal1* 1InstituteofZoology,UniversityofZu¨rich,Zu¨rich,Switzerland,2DivisionofMolecularPsychology,UniversityofBasel,Basel,Switzerland,3LifeScienceTrainingFacility, Biozentrum,UniversityofBasel,Basel,Switzerland,4DivisionofPsychiatryResearch,UniversityofZu¨rich,Zu¨rich,Switzerland,5CenterforIntegrativeHumanPhysiology, UniversityofZu¨rich,Zu¨rich,Switzerland Abstract Background:Whole-genomeassociationstudiesinhumanshaveenabledtheunbiaseddiscoveryofnewgenesassociated withhumanmemoryperformance.However,suchstudiesdonotallowforafunctionalorcausaltestingofnewlyidentified candidategenes.SincepolymorphismsinCalsyntenin2(CLSTN2)showedasignificantassociationwithepisodicmemory performanceinhumans,wetestedtheC.elegansCLSTN2orthologCASY-1forpossiblefunctionsintheassociativebehavior ofC.elegans. Methodology/PrincipalFindings:Usingthreedifferentassociativelearningparadigmsandfunctionalrescueexperiments, weshowthatCASY-1playsanimportantroleduringassociativelearninginC.elegans.Furthermore,neuronalexpressionof humanCLSTN2inC.elegansrescuesthelearningdefectsofcasy-1mutants.Finally,geneticinteractionstudiesandneuron- specificexpressionexperimentssuggestthatCASY-1mayregulateAMPA-likeGLR-1glutamatereceptorsignaling. Conclusion/Significance: Our experiments demonstrate a remarkable conservation of the molecular function of CalsynteninsbetweennematodesandhumansandpointataroleofC.eleganscasy-1inregulatingaglutamatereceptor signalingpathway. Citation: Hoerndli FJ, Walser M, Fro¨hli Hoier E, de Quervain D, Papassotiropoulos A, et al. (2009) A Conserved Function of C. elegans CASY-1 Calsyntenin in AssociativeLearning.PLoSONE4(3):e4880.doi:10.1371/journal.pone.0004880 Editor:BrianD.McCabe,ColumbiaUniversity,UnitedStatesofAmerica ReceivedSeptember4,2008;AcceptedFebruary6,2009;PublishedMarch16,2009 Copyright: