Mechanism of Acetylcholine Receptor Cluster Formation Induced by DC Electric Field 英文参考文献.docVIP

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Mechanism of Acetylcholine Receptor Cluster Formation Induced by DC Electric Field 英文参考文献.doc

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Mechanism of Acetylcholine Receptor Cluster Formation Induced by DC Electric Field 英文参考文献

MechanismofAcetylcholineReceptorClusterFormation InducedbyDCElectricField HailongLukeZhang¤,H.BenjaminPeng* DivisionofLifeScienceandStateKeyLaboratoryofMolecularNeuroscience,TheHongKongUniversityofScienceandTechnology,ClearWaterBay,Kowloon,HongKong Abstract Background: The formation of acetylcholine receptor (AChR) cluster is a key event during the development of the neuromuscular junction. It is induced through the activation of muscle-specific kinase (MuSK) by the heparan-sulfate proteoglycan agrin released from the motor axon. On the other hand, DC electric field, a non-neuronal stimulus, is also highlyeffectiveincausingAChRstoclusteralongthecathode-facingedgeofmusclecells. Methodology/Principal Findings: Tounderstanditsmolecularmechanism,quantumdots(QDs)wereused tofollowthe movementofAChRsastheybecameclusteredundertheinfluenceofelectricfield.FromanalysesoftrajectoriesofAChR movement in the membrane, it was concluded that diffuse receptors underwent Brownian motion until they were immobilizedatsitesofclusterformation.Thissupportsthediffusion-mediatedtrappingmodelinexplainingAChRclustering undertheinfluenceofthisstimulus.DisruptingF-actincytoskeletonassemblyandinterferingwithrapsyn-AChRinteraction suppressedthisphenomenon,suggestingthattheseareintegralcomponentsofthetrappingmechanisminducedbythe electric field. Consistentwith the idea that signaling pathways areactivated by this stimulus, the localizationof tyrosine- phosphorylatedformsofAChRb-subunitandSrc wasobservedatcathodalAChRclusters.Furthermore,disruptingMuSK activitythroughtheexpressionofakinase-deadformofthisenzymeabolishedelectricfield-inducedAChRclustering. Conclusions:TheseresultssuggestthatDCelectricfieldasaphysicalstimuluselicitsmolecularreactionsinmusclecellsin the form of cathodal MuSK activation in a ligand-free manner to trigger a signaling pathway that leads to cytoskeletal assemblyandAChRclustering. Citation:ZhangHL,PengHB(2011)MechanismofAcetylcholineReceptorClusterFormationInducedby