RatNogo-Aisanewlydiscoveredmemberofthereticulonfamilyoftransmembraneproteins.Thisfamilyischaracterizedbythepresenceofanonsignalsequence-containingN-terminus,atopologicallyconservedapproximately200aminoacid(aa)C-terminusthatcontainstwotransmembranedomainsandanER-retentionmotif,andapunctateintracellulardistributionwithintheERthatisreminescentofareticulum.1,2
Images:Nogo-Ainhibitsneuriteoutgrowth.A.Embryonicchickdorsalrootganglion(DRG)cellsexhibitneuriteoutgrowthwhenculturedonnitrocellulose-coatedplatestreatedwithlaminin.PrecoatingsimilarplateswithrecombinantratNogo-A(100µg/mL)completelyinhibitsneuriteoutgrowthfromembryonicchickDRGcells.
Nogo-Ainratexistsinfourisoforms.3-5ThefulllengthratNogo-Ais1163aainlengthandcontainsa989aaN-terminus,a21aatransmembranesegment,a94aaconnecting“loop”,asecond21aatransmembranesegment,anda38aaC-terminus.Threeareasareofparticularinterest.Oneisastretchof66aawithinthe94aatransmembraneconnectingloop(SWISSPROTdefinesthisregionasbeing94aainlengthwhiletheoriginalcloningpapersidentifieditasbeing66aainlength).ThissegmentisreportedtobindtotheGPI-linkedNogoreceptor/p75complexonaxonsandinducegrowthconecollapse.6-8 TwootherareasintheN-terminushavealsobeendiscoveredtohavebioactivity.6,9,10 TheexacttopologyofNogo-Aisunclear.Withtwotransmembranesegments,theN-andC-terminimaybeextracellularwiththe“loop”regionintracellular,orthesituationcouldbereversed.11,12Alternatively,theloopregionandN-terminusmaybeonthesamesideofthemembrane.6Nogo-Aisexpressedinneurons,endothelialcells.oligodendrocytes,fibroblastsandmyoblasts.10,13,14RatNogo-Ais78%aaidenticaltohumanNogo-Aoverall,with98%aaidenticalintheloopregionand81%aaidentityintheaa544-725segment.
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