ThisSnapShotoriginallyappearedintheOctober19,2007issueofCell.SnapShot:NuclearTransportElizabethJ.Tran,TimothyA.Bolger,andSusanR.WenteCellandDevelopmentalBiology,VanderbiltUniversityMedicalCenter,Nashville,TN37232,USAExchangeofmacromoleculesbetweenthenucleusandthecytoplasmoccursthroughnuclearporecomplexes(NPCs),largeproteinaceousstructuresembeddedwithinthenuclearenvelope.Smallmolecules(<30kDa)canpassivelydiffusethroughNPCs.Nucleartransportreceptorsarerequiredtofacilitateimportandexportoflargemolecules(>30kDa).Thisincludesthekaryopherin-β(Kapβ)receptorfamilywhereineachassociatesdirectlywiththeNPCandhascargobindingcontrolledbytheasymmetricdistributionofRan-GTPandtheRancycle(seeFigure).NuclearlocalizationoftheRanguanine-nucleotideexchangefactor(Ran-GEF,Prp20inS.cerevisiae)viachromatinassociationmaintainshighconcentrationsofRan-GTPinthenucleus.Conversely,Ran-GDPpredominatesinthecytoplasmthroughthecombinedactionofcytoplasmicallylocalizedRan-BindingProtein1(RanBP1,Yrb1inS.cerevisiae)andRanGTPase–ActivatingProtein(Ran-GAP,Rna1inS.cerevisiae).Duringimport,KapβreceptorsinteractwithcytoplasmiccargosandtraversetheNPC.Inthenucleus,Ran-GTPbindstotheimportingKapβandtriggerscargorelease.Conversely,duringexport,Ran-GTPstabilizestheassociationofKapβreceptorswithnuclearcargo.HydrolysisofGTPtoGDPatthecytoplasmicNPCfacepromotesdisassemblyoftheexportreceptor-cargocomplex.Transportreceptorsarecategorizedbasedontransportdirection,theuseofcargoadaptors,andtransportofspecializedcargosuchasRan-GDP,ribosomes,and/ormRNA.(I)Importreceptorcomplexeswithadaptors:Kap60-Kap95(importin-α-importin-βinmetazoa)istheprototypicalimportreceptor.Cargowithaclassicalnuclearlocalizationsignal(cNLS)isrecognizedbytheadaptorKap60,whichbindsthereceptorKap95.Whereasyeasthasonlyoneimportin-α,metazoanshaveseveralimportin-αhomologs(notshown).(II)Importreceptorsthatbindcargodirectly:ManyKapβs,includingKap104,canbinddirectlytotheircargo.(III)Bidirectionaltransportreceptors:TheyeastreceptorMsn5andthemammalia...
