NogginisasecretedhomodimericglycoproteinthatisanantagoNISTofbonemorphogeneticproteins(BMPs).1,2HumanNogginCDNAencodesa232aminoacid(aa)precursorprotein;cleavageofa19aasignalpeptidegeneratesthe213aamatureproteinwhichcontainsanN-terminalacidicregion,acentralbasicheparin-bindingsegmentandaC-terminalcysteine-knotstructure.2SecretedNogginprobablyremainsclosetothecellsurfaceduetoitsbindingofheparin-containingproteoglycans.3Nogginisveryhighlyconservedamongvertebrates,suchthatmaturehumanNogginshares99%,99%,98%,97%and89%aasequenceidentitywithmouse,rat,bovine,equineandchickNoggin,respectively.NogginbindssomeBMPssuchasBMP-4withhighaffinityandotherssuchasBMP-7withloweraffinity,antagonizingBMPbioactivitiesbyblockingepitopesonBMPsthatareneededforbindingtobothtypeIandtypeIIreceptors.2,4Duringembryogenesis,NogginantagonizesspecificBMPsatdefinedtimesduringneuraltube,somiteandcardiomyocytegrowthandpatterning.5-7Duringskeletaldevelopment,Nogginpreventschondrocytehyperplasia,thusallowingproperformationofjoints.4Mutationswithinthecysteine-knotregionofhumanNogginarelinkedtomultipletypesofskeletaldysplasiasthatresultinapicaljointfusions.8Nogginisexpressedindefinedareasoftheadultcentralnervoussystemandperipheraltissuessuchaslung,skeletalmuscleandskin.1Duringcultureofhumanembryonicstemcells(hESC)withoutfeederlayersorconditionedmedium,butwithadditionofFGFbasic,additionofNoggintoantagonizeBMPactivityallowshESCtomaintaintheirundifferentiated,pluripotentstate.9,10
References:
1.Valenzuela,D.M.etal.,1995,J.Neurosci.15:6077-6084.6.Itsykson,P.etal.,2005,Mol.Cell.Neurosci.30:24-36.
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