Reelinisanextracellularproteinsecretedbyneurons.ReelermicewithadefectiveReelingeneexhibitneuronalabnormalitiesindevelopment.MicethatareheterozygousfortheReelinknockouthaveneuroanatomicalandbehavioraltraitssimilartothoseofschizophreniapatients,suggestingthatmicewithadeficiencyinReelinmayprovideausefulmodelforschizophrenia.Reelinproteinmaybeinvolvedincognitivefunctioninadultsaswellasplayingaroleinthedevelopmentalorganizationofneuronsinthecortex.MultiplecellsurfacereceptorstransduceReelinsignalingintoneurons.OneclassofReelinreceptorincludestheVLDLreceptorandtheApoER2.TheintracellularadaptorDab1bindstotheVLDLreceptorandApoER2receptorthroughanNPxYmotifandisinvolvedintransmissionofReelinsignalsthroughtheselipoproteinreceptors.MutationofthemDab1geneinmicecreatesaphenotypeidenticaltoReelermice,supportingtheroleofthiscytoplasmicfactorinsignalingdownstreamfromReelin.AnotherclassofreceptorforReelinisthecadherin-relatedneuronalreceptors,CNRreceptors.ReelinsignalingthroughseveraldifferentCNRreceptorsactivatestheFyntyrosinekinases.ReelinstimulatesphosphorylationofDab1andDab1appearstolinkReelinsignalingwithtyrosinekinases.Disruptionofthep35andCdk5genesinmiceindicatesthatcdk5isalsoinvolvedintheroleofReelininneuronaldevelopment.

Contributor:GlennCroston,PhD

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