Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons 英文参考文献.docVIP

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Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons 英文参考文献.doc

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Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons 英文参考文献

Protein4.1BContributestotheOrganizationof PeripheralMyelinatedAxons CarmenCifuentes-Diaz1,2,3.,FabriceChareyre4.¤a,MartaGarcia1,2,3.,Je′ro?meDevaux5,Miche`le Carnaud1,2,3,Gre′goireLevasseur1,2,3¤b,MichikoNiwa-Kawakita4,SheilaHarroch6 ,Jean-Antoine Girault1,2,3*,MarcoGiovannini4¤a,LaurenceGoutebroze1,2,3 1Inserm,UMR-S839,Paris,France,2Universite′ PierreetMarieCurie(UPMC),Paris,France,3InstitutduFera` Moulin,Paris,France,4Inserm,U674,InstitutUniversitaire d’He′matologie,Paris,France,5De′partementdeSignalisationNeuronale,CRN2M,UMR6231,CNRS,Universite′delaMe′diterrane′e-Universite′PaulCe′zanne,IFRJeanRoche, Marseille,France,6De′partement deNeuroscience,InstitutPasteur,Paris,France Abstract Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors includinginteractionsbetweenthecytoskeletonandmembraneproteins.Inmanycelltypes,membersoftheprotein4.1 familyplayanimportantroleintetheringthecorticalactin-spectrincytoskeletontotheplasmamembrane.Protein4.1Bis localizedinmyelinatedaxons,enrichedinparanodalandjuxtaparanodalregions,andalsoallalongtheinternodes,butnot at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied4.1Bknockoutmice.Thesemicedisplayedamildlyimpairedgaitandmotility.Whereasnodeswereunaffected,the distributionofCaspr/paranodin,whichanchors4.1Btothemembrane,wasdisorganizedinparanodalregionsanditslevels weredecreased.Injuxtaparanodes,theenrichmentofCaspr2,whichalsointeractswith4.1B,andoftheassociatedTAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves andpreterminal motor axonsweredysmorphicinskeletalmuscle.bIIspectrinenrichmentwasdecreasedalongtheaxol