Reelinisanextracellularproteinsecretedbyneurons.ReelermicewithadefectiveReelingeneexhibitneuronalabnormalitiesindevelopment.MicethatareheterozygousfortheReelinknockouthaveneuroanatomicalandbehavioraltraitssimilartothoseofschizophreniapatients,suggestingthatmicewithadeficiencyinReelinmayprovideausefulmodelforschizophrenia.Reelinproteinmaybeinvolvedincognitivefunctioninadultsaswellasplayingaroleinthedevelopmentalorganizationofneuronsinthecortex.MultiplecellsurfacereceptorstransduceReelinsignalingintoneurons.OneclassofReelinreceptorincludestheVLDLreceptorandtheApoER2.TheintracellularadaptorDab1bindstotheVLDLreceptorandApoER2receptorthroughanNPxYmotifandisinvolvedintransmissionofReelinsignalsthroughtheselipoproteinreceptors.MutationofthemDab1geneinmicecreatesaphenotypeidenticaltoReelermice,supportingtheroleofthiscytoplasmicfactorinsignalingdownstreamfromReelin.AnotherclassofreceptorforReelinisthecadherin-relatedneuronalreceptors,CNRreceptors.ReelinsignalingthroughseveraldifferentCNRreceptorsactivatestheFyntyrosinekinases.ReelinstimulatesphosphorylationofDab1andDab1appearstolinkReelinsignalingwithtyrosinekinases.Disruptionofthep35andCdk5genesinmiceindicatesthatcdk5isalsoinvolvedintheroleofReelininneuronaldevelopment. Contributor:GlennCroston,PhD REFERENCES:Ballmaier,M.,Zoli,M.,Leo,G.,Agnati,L.F.,Spano,P.(2002)Preferentialalterationsinthemesolimbicdopaminepathwayofheterozygousreelermice:anemerginganimal-basedmodelofschizophrenia.Eur.J.Neurosci.15(7),1197-1205Fatemi,S.H.,Kroll,J.L.,Stary,J.M.(2001)AlteredlevelsofReelinanditsisoformsinschizophreniaandmooddisorders.Neuroreport.12(15),3209-15Hong,S.E.etal.(2000)AutosomalrecessivelissencephalywithcerebellarhypoplasiaisassociatedwithhumanRELNmutations.Nat.Genet.26(1),93-6Howell,B.W.etal.(2000)Dab1tyrosinephosphorylationsitesrelaypositionalsignalsduringmousebraindevelopment.Curr.Biol.10(15),877-85Howell,B.W.,Gertler,F.B.,Cooper,JA.(1997)Mousedisabled(mDab1):aSrcbindingproteinimplicatedinneuronaldevelopment.EMBOJ.16(1),121-32Ohshima,T.etal.(2001)Synergisticcontributionsofcyclin-dependantkinase5/p35andReelin/Dab1tothepositioningofcorticalneuronsinthedevelopingmousebrain.ProcNatlAcadSciUSA98(5):2764-9Rice,D.S.etal.(1998)Disabled-1actsdownstreamofReelininasignalingpathwaythatcontrolslaminarorganizationinthemammalianbrain.Development125(18),3719-29Senzaki,K.,Ogawa,M.,Yagi,T.(1999)ProteinsoftheCNRfamilyaremultiplereceptorsforReelin.Cell99(6),635-47SmithD.,TsaiL.Cdk5behindthewheel:aroleintraffickingandtransport?TrendsinCellBIOLOGy2002Vol12(1):pp28-36TromMSDorff,M.etal.(1999)Reeler/Disabled-likedisruptionofneuronalmigrationinknockoutmicelackingtheVLDLreceptorandApoEreceptor2.Cell97(6),689-701