Site Specific Cleavage Mediated by MMPs Regulates Function of Agrin 英文参考文献.docVIP

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Site Specific Cleavage Mediated by MMPs Regulates Function of Agrin 英文参考文献.doc

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Site Specific Cleavage Mediated by MMPs Regulates Function of Agrin 英文参考文献

SiteSpecificCleavageMediatedbyMMPsRegulates FunctionofAgrin TrusharR.Patel1.,GeorginaButler2.,AinsleyMcFarlane1,IreneXie1,ChristopherM.Overall2, Jo¨rgStetefeld1* 1DepartmentofChemistry,UniversityofManitoba,Winnipeg,Manitoba,Canada,2CentreforBloodResearch,UniversityofBritishColumbia,Vancouver,BritishColumbia, Canada Abstract Background: Agrin is the key inducer of postsynaptic differentiations at the neuromuscular junction. The multidomain heparansulfateproteoglycanismediatingviaitsN-terminalsegmenttheinteractionwithlaminin,whereastheC-terminal portion is responsible for Dystroglycan binding and clustering of the Acetylcholine receptor. Matrix metalloproteinases (MMP) are known to play essential roles in matrix remodeling, degradation and regulation of extracellular signaling networks. PrincipalFindings:Site-specificprocessingofAgrinprovideskeyinsightintoregulatoryeffectsofMatrixmetalloproteinases (MMPs).Here,wepresentadetailedstudyofagrinprocessingbydifferentMMPstogetherwithamolecularunderstanding ofbindingandcleavageatbothterminalfragments.ThedatasuggestforaregulatoryeffectofMMPcleavageatparticularly importantfunctionalsitesofagrin.Cleaveof agrinabolishes theagrin-laminincomplexformationandtheAcetylcholine receptorclusteringattheneuromuscularjunction. Conclusion/Significance: Agrin is a target of specific MMP processing resulting in agrin subfragments with different regulatoryactivities.MMPprocessingisapowerfultooltoregulateextracellularsignalingnetworks. Citation:PatelTR,ButlerG,McFarlaneA,XieI,OverallCM,etal.(2012)SiteSpecificCleavageMediatedbyMMPsRegulatesFunctionofAgrin.PLoSONE7(9): e43669.doi:10.1371/journal.pone.0043669 Editor:Shu-minDuan,ZhejiangUniversitySchoolofMedicine,China ReceivedApril13,2012;AcceptedJuly23,2012;PublishedSeptember11,2012 Copyright: ? 2012 Patel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,provided