SnapShot:TightandAdherensJunctionSignalingJenniferL.HarderandBenMargolisDepartmentsofInternalMedicineandBiologicalChemistry,UniversityofMichigan,AnnArbor,MI48109,USASeeonlineversionforlegend,abbreviations,andreferences.1118Cell133,June13,2008©2008ElsevierInc.DOI10.1016/j.cell.2008.06.0021118.e1Cell133,June13,2008©2008ElsevierInc.DOI10.1016/j.cell.2008.06.002SnapShot:TightandAdherensJunctionSignalingJenniferL.HarderandBenMargolisDepartmentsofInternalMedicineandBiologicalChemistry,UniversityofMichigan,AnnArbor,MI48109,USASignalingpathwaysconverginguponandemanatingfromadherensjunctions(AJs)andtightjunctions(TJs)affectmanycellularfunctions,includingcytoskeletaldynamics,polarizedvesicletrafficking,proteinsynthesis,andproliferation.Manypathologicprocessestargetjunctionalproteins,resultinginthedisassemblyofjunc-tionsandbreakdownoftissueintegrity.Assignalingpathwaysandproteincomponentsofjunctionsvaryamongorganisms,thisSnapShothighlightsthosepathwaysestablishedinmammalianepithelia.AssemblyofApicalJunctionsandPolarizedMembranesTransdimerizationofheterophilicnectinsbetweenadjacentcellsisacriticaleventleadingtothedevelopmentofAJs,TJs,andpolarizedmembranedomains.(1)Uponas-sociationwithdimerizednectin,integrinαVβ3initiatesasetofsignalingeventsinvolvingc-Src,whichresultsintheactivationofRap1,Cdc42,andRac.Subsequently,Rap1complexeswithafadinandp120ctnresultinginstabilizationofE-cadherinatthecellsurfacefollowedbyrecruitmentofβ-andα-cateninandFerkinase.E-cadherinstabiliza-tionalsotriggersdeliveryofoccludinandclaudintonascentTJsattheapicalsideofAJs.Concurrently,nectinaccumulatesJAMthroughitsinteractionwithafadinandZO1,developingaplatformforPar3localization.Par6andaPKCjoinPar3afterLIMKisreleased,aneventtriggeredbyphosphorylationofPar3downstreamofEGFRactivation.(2)aPKCatnascentTJscontributestopolarizationoftheapicalmembranebytargetingspecificproteinsforexclusionfromthisregion.PhosphorylationofPar1andmLglbyaPKCresultsintheirrecruitmenttothenascentBLM.AttheBLM,Par1andmLglinhibiti...
