Nuclear Transport.PDF

Transport Complex CategoryS.cerevisiae Karyopherins&Other ReceptorsCargo(s)EssentialMetazoan Karyopherins&Other ReceptorsCargo(s)ImportIKap95Kap60 adaptor for cNLS proteins YesImportin-b1Importin-a adaptor for cNLS proteins,Snurportin adaptor for U snRNPsIIKap95YesImportin-b1SREBP-2,HIV Rev and TAT,Cyclin BKap104Nab2,Hrp1(mRNA-binding proteins)t.s.Transportin or Transportin 2PY-NLS-containing proteins,mRNA-binding proteins,histones,ribosomal proteinsKap123SRP proteins,histones,ribo-somal proteinsNoImportin 4histones,ribosomal protein S3a,Transition Protein 2Kap111/Mtr10Npl3(mRNA-binding protein),tRNAst.s.Transportin SR1 or SR2SR proteins,HuRKap121/Pse1ribosomal proteins,Yra1,Spo12,Ste12,Yap1,Pho4,histonesYesImportin 5/Importin-b3/RanBP5histones,ribosomal proteinsKap119/Nmd5ribosomal pro-teins,histones,Hog1,Crz1,Dst1NoImportin 7GR,ribosomal pro-teins,Smad,ERKKap108/Sxm1Lhp1,ribosomal proteinsNoImportin 8SRP19,SmadKap114TBP,histones,Nap1,Sua7NoImportin 9histones,ribosomal proteinsKap122/Pdr6Toa1 and Toa2,TFIIANoKap120Rpf1 NoImportin 11UbcM2,rpL12Ntf2Ran/Gsp1(GDP-bound form)YesNTF2Ran(GDP-bound form)Import/ExportIIIKap142/Msn5Replication pro-tein A(import),Pho4,Crz1,Cdh1(export)NoImportin 13UBC9,Y14(import),eIFIA(export)ExportIVCrm1/Xpo1Leucine-rich NES sequencesYesCRM1/Exportin 1Leucine-rich NES sequencesKap109/Cse1Kap60/Srp1YesCASImportin-a family membersKap127/Los1tRNAsNoExportin-ttRNAsExportin 4eIF5AExportin 5pre-miRNAExportin 6Profilin,actinRanBP16/Exportin 7p50-RhoGAPVCrm1/Xpo1Nmd3 adaptor for 60S ribosomal subunitYesCRM1/Exportin 1NMD3 adaptor for 60S ribosomal subunitMex67-Mtr260S via 5S rRNAYesArx160S ribosomal subunitNoCrm1/Xpo1Ltv1 putative adaptor for 40S ribosomal subunitYesCRM1/Exportin 140S ribosomal subunitVIMex67-Mtr2Npl3,Yra1,and Hpr1 adaptors for mRNAYesTAP/NXF1-p15/NXT1REF/Aly adaptor for mRNASnapShot:Nuclear TransportElizabeth J.Tran,Timothy A.Bolger,and Susan R.WenteCell and Developmental Biology,Vanderbilt University Medical Center,Nashville,TN 37232,USA420 Cell 131,October 19,2007 2007 Elsevier Inc.DOI 10.1016/j.cell.2007.10.015See online version for legend,references,and abbreviations.SnapShot:Nuclear TransportElizabeth J.Tran,Timothy A.Bolger,and Susan R.WenteCell and Developmental Biology,Vanderbilt University Medical Center,Nashville,TN 37232,USAExchange of macromolecules between the nucleus and the cytoplasm occurs through nuclear pore complexes(NPCs),large proteinaceous structures embedded within the nuclear envelope.Small molecules(30 kDa).This includes the karyopherin-b(Kapb)receptor family wherein each associates directly with the NPC and has cargo binding controlled by the asymmetric distribution of Ran-GTP and the Ran cycle(see Figure).Nuclear localization of the Ran guanine-nucleotide exchange factor(Ran-GEF,Prp20 in S.cerevisiae)via chromatin association maintains high concentrations of Ran-GTP in the nucleus.Conversely,Ran-GDP predominates in the cytoplasm through the com-bined action of cytoplasmically localized Ran-Binding Protein 1(RanBP1,Yrb1 in S.cerevisiae)and Ran GTPaseActivating Protein(Ran-GAP,Rna1 in S.cerevisiae).During import,Kapb receptors interact with cytoplasmic cargos and traverse the NPC.In the nucleus,Ran-GTP binds to the importing Kapb and triggers cargo release.Conversely,during export,Ran-GTP stabilizes the association of Kapb receptors with nuclear cargo.Hydrolysis of GTP to GDP at the cytoplasmic NPC face promotes disassembly of the export receptor-cargo complex.Transport receptors are categorized based on transport direction,the use of cargo adaptors,and transport of spe-cialized cargo such as Ran-GDP,ribosomes,and/or mRNA.(I)Import receptor complexes with adaptors:Kap60-Kap95(importin-a-importin-b in metazoa)is the prototypical import receptor.Cargo with a classical nuclear local-ization signal(cNLS)is recognized by the adaptor Kap60,which binds the receptor Kap95.Whereas yeast has only one importin-a,metazoans have several importin-a homologs(not shown).(II)Import receptors that bind cargo directly:Many Kapbs,including Kap104,can bind directly to their cargo.(III)Bidirectional transport receptors:The receptor Msn5 has the striking capacity to function in both import and export.(IV)Export receptor complexes:The first identified export receptor,Crm1,recognizes leucine-rich nuclear export sequences(NES)in cargo proteins.(V)Export of ribosomal subunits:Large cargos,such as ribosomal subunits,require multiple receptors for transport.Export of the assembled 60S subunit requires Crm1(with the adaptor Nmd3)and,in S.cerevisiae,the Mex67-Mtr2 heterodimer as well as Arx1.Export of the 40S subunit also requires Crm1 and possibly an adap-tor,Ltv1.(VI)Export of mRNA:Export of most mRNA is Ran independent and,instead,requires the nonkaryopherin Mex67-Mtr2(TAP/NXF1 and p15/NXT1 in metazoans,re-spectively).Mex67-Mtr2 binds mRNA thorough association with mRNA-binding proteins,or some metazoan mRNAs can recruit TAP/NXF1 by directly binding a specific RNA element,the CTE(not shown).CTEs are also present in some viral RNAs.Directionality of mRNA export is determined by the ATPase Dbp5,whose activation is controlled by spatially restricted inositol hexakisphosphate(IP6)-bound Gle1.Consensus SequencescNLS:PKKKRKV(monopartite)or KRX(1012)KRRK(bipartite);PY-NLS:(G/S/A)X(510)(R/H/K)X(25)PY(hPY-NLS)or basic-enriched(58)X(27)(R/H/K)X(25)PY(bPY-NLS),denotes hydrophobic residue;NES:(L/V)X(23)(/F)X(23)LX,denotes large aliphatic residue(I,V,L,M).AbbreviationsNLS,nuclear localization signal;NES,nuclear export signal;t.s.,temperature sensitive;U snRNP,uridine-rich small nuclear ribonucleoprotein complex;SR,serine/ar-ginine-rich;TBP,TATA-binding protein;SRP,signal recognition particle;hnRNP,heterogeneous nuclear ribonucleoprotein.REfEREnCESBradatsch,B.,Katahira,J.,Kowalinski,E.,Bange,G.,Yao,W.,Sekimoto,T.,Baumgartel,V.,Boese,G.,Bassler,J.,Wild,K.,et al.(2007).Arx1 functions as an unortho-dox nuclear export receptor for the 60S 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