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1、JournalofCellularBiochemistry100:12881300(2007)PalladinRegulatesCellandExtracellularMatrixInteractionThroughMaintainingNormalActinCytoskeletonArchitectureandStabilizingBeta1-Integrin1,4132,331Xue-SongLiu,Hui-JunLuo,HuaYang,LongWang,HuiKong,Yue-EJin,11211,2,3FangWang,Ming-MinGu,ZhuChen,Zhen-YuLu,and
2、Zhu-GangWang*1LaboratoryofGeneticEngineering,DepartmentofMedicalGenetics,InstituteofHealthSciences,ShanghaiJiaoTongUniversityMedicalSchool&ShanghaiInstitutesforBiologicalSciencesofChineseAcademyofSciences,Shanghai200025,PRChina2StateKeyLaboratoryofMedicalGenomics,Rui-jinHospital,ShanghaiJiaoTongUni
3、versityMedicalSchool,Shanghai200025,PRChina3ShanghaiResearchCenterforModelOrganisms,Shanghai201203,PRChina4GraduateSchoolofChineseAcademyofSciences,Shanghai200025,PRChinaAbstractCellandextracellularmatrix(ECM)interactionplaysanimportantroleindevelopmentandnormalcellularfunction.Celladhesionandcells
4、preadingonECMaretwobasiccellularbehaviorsrelatedtocell-ECMinteraction.Hereweshowthatpalladin,anovelactincytoskeleton-associatedprotein,isactivelyinvolvedintheregulationofcell-ECMinteraction.Itwasfoundthatpalladin-deficientmouseembryonicfibroblasts(MEFs)displaydecreasedcelladhesionandcompromisedcellsp
5、readingonvariousECMs.Disorganizedactincytoskeletonarchitecturecharacterizedbyfaintstressfibers,lesslamellipodiaandfocaladhesionscanaccountfortheweakenedcell-ECM/interactioninpalladinMEFs.Furthermore,decreasedpolymerizedfilamentactinandincreasedglobularactincanbe/observedinpalladinMEFs,stronglysug
6、gestingthatpalladinisessentialfortheformationorstabilizationofpolymerizedfilamentactin.Elevatedphospho-cofilinlevelandproperresponsesincofilinphosphorylationtoeitherRho//signalagonistorantagonistinpalladinMEFsindicatethatdisruptedstressfibersinpalladinMEFsisnotassociatedwithcofilinphosphorylation.Mo
7、reinterestingly,theproteinlevelofECMreceptorb1-integrinisdramaticallydecreasedinMEFslackingpalladin.Down-regulationofb1-integrinproteincanberestoredbyproteasomeinhibitorMG-132treatment.Allthesedataimplicate