Anopheles gambiae APL1 Is a Family of Variable LRR Proteins Required for Rel1-Mediated Protection from the Malaria Parasite, Plasmodium berghei 英文参考文献.docVIP

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Anopheles gambiae APL1 Is a Family of Variable LRR Proteins Required for Rel1-Mediated Protection from the Malaria Parasite, Plasmodium berghei 英文参考文献.doc

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Anopheles gambiae APL1 Is a Family of Variable LRR Proteins Required for Rel1-Mediated Protection from the Malaria Parasite, Plasmodium berghei 英文参考文献

AnophelesgambiaeAPL1IsaFamilyofVariableLRR ProteinsRequiredforRel1-MediatedProtectionfromthe MalariaParasite,Plasmodiumberghei MichelleM.Riehle1.,JiannongXu1.¤,BrianP.Lazzaro2,SusanM.Rottschaefer2,BoubacarCoulibaly3, MadjouSacko3,OumouNiare3,IsabelleMorlais4,SekouF.Traore3,KennethD.Vernick1,5* 1DepartmentofMicrobiology,UniversityofMinnesota,SaintPaul,Minnesota,UnitedStatesofAmerica,2DepartmentofEntomology,CornellUniversity,Ithaca,New York, United States of America, 3Malaria Research andTraining Center, University ofBamako, Bamako,Mali, 4Laboratoire de Recherche sur lePaludisme, Institut de recherchepourlede′veloppementIRD-OCEAC,Yaounde′,Cameroun,5UnitofInsectVectorGeneticsandGenomics,DepartmentofParasitologyandMycology,CNRSUnit URA3012:Hosts,VectorsandInfectiousAgents,InstitutPasteur,Paris,France Abstract Background: We previously identified by genetic mapping an Anopheles gambiae chromosome region with strong influenceovertheoutcomeofmalariaparasiteinfectioninnature.Candidategenestudiesinthegeneticinterval,including functionaltestsusingtherodentmalariaparasitePlasmodiumberghei,identifiedanovelleucine-richrepeatgene,APL1 ,with functionalactivityagainstP.berghei. Principal Findings:Manualreannotation now revealsAPL1 tobeafamilyofat least3independently transcribed genes, APL1A,APL1B,andAPL1C.FunctionaldissectionindicatesthatamongthethreeknownAPL1familymembers,APL1Caloneis responsibleforhostdefenseagainstP.berghei.APL1CfunctionswithintheRel1-Cactusimmunesignalingpathway,which regulates APL1C transcript and protein abundance. Gene silencing of APL1C completely abolishes Rel1-mediated host protection against P. berghei, and thus the presence of APL1C is required for this protection. Further highlighting the influenceofthis chromosomeregion,allelichaplotypesat theAPL1locusaregenetically associatedwithandhavehigh explanatorypowerforthesuccessorfailureofP.bergheiparasiteinfection. Conclusions: APL1C functions as a required transducer of Rel1-dependent immune signal(