1378Cell131,December28,2007©2007ElsevierInc.DOI10.1016/j.cell.2007.12.011Seeonlineversionforlegend,abbreviations,andreferences.SnapShot:NoncanonicalWntSignalingPathwaysMikhailV.Semenov,1RaymondHabas,2BryanT.MacDonald,1andXiHe11Children’sHospitalBoston,HarvardMedicalSchool,Boston,MA02115,USA;2UniversityofMedicineandDentistryofNewJersey,Piscataway,NJ08854,USA1378.e1Cell131,December28,2007©2007ElsevierInc.DOI10.1016/j.cell.2007.12.011SnapShot:NoncanonicalWntSignalingPathwaysMikhailV.Semenov,1RaymondHabas,2BryanT.MacDonald,1andXiHe11TheF.M.KirbyNeurobiologyCenter,Children’sHospitalBoston,HarvardMedicalSchool,Boston,MA02115,USA2DepartmentofBiochemistry,UniversityofMedicineandDentistryofNewJersey,Piscataway,NJ08854,USANoncanonicalWntsignalingisdefinedhereasWnt-orFz-initiatedsignalingthatisindependentofβ-catenintranscriptionalfunction.NoncanonicalWntpathwaysarediverseandinmanycaseslesscharacterized/defined.Theyaregroupedintoseveralcategoriesforclarityandsimplicity.Suchclassificationsarenotrigidasthesepathwayslikelyoverlapwithorintersectoneanotherandareevolving.(A)Wnt/PCP(planarcellpolarity)signaling.VertebrateWnt5aandWnt11initiatesignalingviaFz,whichmayactivatetrimericGproteinsandDvl(likelyviaphosphory-lation),andtheassemblyofDvl/effectorcomplexes.MultiplepathwaysdownstreamofDvlregulateactincytoskeleton/celladhesion.TheDvl-Daam1-RhoAcomplexactivatesRhoA,whichleadstoRockkinaseactivationandMRLCphosphorylation;Dvl-Rac1complexactivatesJNKkinase,whichmayphosphorylateCapZIP/Dub;DvlandXRNF185(anE3ligase)downregulatePXNproteinlevel.DvlrecruitmenttothemembranebyFzisregulatedbykinasesincludingPar1,CK1ε,andPKCδ.Dvl-bindingproteins/complexes—includingDiv,Inv(relatedtoDrosophilaDgo),endocyticb-arr2,andtheAP2complex—regulateDvlPCPfunction.ProteoglycanslikeGlypican4/KnypekandSyndicanandprotocadherinPAPCalsohaverolesinPCPsignaling.RTK7isinvolvedinPCPsignalingduringneuraltubeclosure.(A1)PolarizedlocalizationofPCPproteinsismaintainedby,andrequiredfor,PCPsignalinginDrosophilawing...
