Contactin4(CNTN4),alsoknownasBIG2(BrainderivedImmunoglobulinSuperfamilymolecule2),isanaxonalcelladhesionmoleculethatbelongstothecontactinfamily,asubfamilyoftheIgsuperfamily(13).Thecontactinfamilycomprisessixmembers(CNTN1/F3,CNTN2/TAG1,CNTN3/BIG1,CNTN4/BIG2,CNTN5/NB2andCNTN6/NB3)andarecharacterizedbythepresenceofsixIglikedomains,fourfibronectintypeIIIlikerepeats,andaglycosylphosphatidylinositol(GPI)anchoringdomain.ContactinfamilyproteinsexistasmembraNEBoundproteins,butcanalsobereleasedassolubleproteinsbyGPIspecificphospholipaseD.SolubleContactinsarefunctionslproteinsthatareabletopromoteneuriteoutgrowth.
Image:Rathippocampalneuronsgrownonmicroplatespre-coatedwithhumanContactin-4
HumanCNTN4hasbeenmappedtochromosome3p26p25.Threealternativetranscriptsof CNTN4,encodingisoformsa,b,andcprecursorproteinscontaining1026,282,and698aminoacid(aa)residues,respectively,havebeendescribed.HumanCNTN4isoformashares94%aasequenceidentitywithitsrathomolog.Italsosharesfrom4466%aasequenceidentitywithotherCNTNfamilymembers.CNTNfamilymembersdisplayoverlappingbutdistinctexpressionpatterns.CNTN4expressionisdetectedinmultipleorgansincludingbrains,pancreas,kidney,aorta,smallintestine,thyroid,uterusandtestis.However,expressionofthe282aaisoformbisprimarilyrestrictedtothebrain.CNTN4hasbeensuggestedtoplayimportantrolesintheformationofneuronalnetworksduringnervoussytemsdevelopment.DisruptionofCNTN4hasbeenimplicatedinthe3pdeletionsyndromecharacterizedbygrowthfailure,developmentaldelay,andmentalretardation.CNTN4expressionisinducedinhumanneuroblastomatumorcellstreatedwithretinoicacidandmayberesponsIBLeforthetheneuritogenicresponseoftumorcellstoretinoids.RecombinantCNTN4showsinvitroneuriteoutgrowthpromotingactivity.
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