AgrinDok-7AChRRapsynStabilizesdifferentiationAntagonizesdifferentiationCortactin,α-actininACF7,Actin,MyosinRhoGTPasesDvl,Pak,Tid1Abl1/2AChRMuSKLrp4AChEUtrophinBoneMuscleMusclefibersMOTORAXONTERMINALCYTOSOLAChCrk/Crk-LRapsynRapsynStabilizesdifferentiationRhoGTPasesCrk/Crk-LLrp4MuSKPPRapsynRapsynETSErm/GABP/ERGJNKMotoraxonsapproachmusclesthatareprepatternedNucleusAChRtranscriptionAChRclusterAChRclusterAChRclusterMuSKLrp4InnervationMotoraxonsMotoraxonsAgrinDok-7StabilizesdifferentiationAChRDok-7StabilizesdifferentiationLrp4Erm/GABP/ERGErm/GABP/ERGPAChRPPPPCrk/Crk-LPAgrinMuSKDok-7RapsynAChRAChEChATNav1.4Auto-antibodiestoAChRsAuto-antibodiestoMuSKHypomorphicmutationsinthesegenesimpairpostsynapticdifferentiation.ThenumberofAChRsatsynapsesisreduced,whichcompromisesthereliabilityofsynaptictransmissionandleadstomuscleweaknessandfatigue.Mutationsinthesegenesimpairsynaptictransmission,leadingtomuscleweaknessandfatigue.ChATencodestheenzymeforsynthesizingACh,andNav1.4encodesavoltage-activatedsodiumchannelexpressedinskeletalmuscle.CauseaccelerateddegradationofAChRsandstructuraldisorganizationofthesynapse,leadingtoMyastheniaGravisCausestructuraldisorganizationofthesynapse,leadingtoMyastheniaGravis.CONGENITALMYASTHENIAMYASTHENIAGRAVISMUSCLEMotoraxonterminalMusclemembraneSynapticcleftMitochondrionNEUROMUSCULARJUNCTIONNMJDiseasesSeeonlineversionforlegendandreferences.826Cell144,March4,2011©2011ElsevierInc.DOI10.1016/j.cell.2011.02.037SnapShot:NeuromuscularJunctionStevenJ.BurdenSkirballInstituteofBiomolecularMedicine,NewYorkUniversityMedicalSchool,NewYork,NY10016,USA826.e1Cell144,March4,2011©2011ElsevierInc.DOI10.1016/j.cell.2011.02.037SnapShot:NeuromuscularJunctionStevenJ.BurdenSkirballInstituteofBiomolecularMedicine,NewYorkUniversityMedicalSchool,NewYork,NY10016,USATheneuromuscularsynapse—theconnectionbetweenmotorneuronsandskeletalmuscle—controlsourabilitytomoveandbreath,andthus,itisessentialforsurvival.Motornerveterminalsreleasetheneurotransmitteracetylcholine(ACh),whichdif...
