Introduction to Nucleocytoplasmic Transport

Molecules and Mechanisms
  • Reiner Peters
Part of the Methods in Molecular Biology™ book series (MIMB, volume 322)


Nucleocytoplasmic transport, the exchange of matter between nucleus and cytoplasm, plays a fundamental role in human and other eukaryotic cells, affecting almost every aspect of health and disease. The only gate for the transport of small and large molecules as well as supramolecular complexes between nucleus and cytoplasm is the nuclear pore complex (NPC). The NPC is not a normal membrane transport protein (transporter). Composed of 500 to 1000 peptide chains, the NPC features a mysterious functional duality. For most molecules, it constitutes a molecular sieve with a blurred cutoff at approx 10 nm, but for molecules binding to phenylalanine-glycine (FG) motifs, the NPC appears to be a channel of approx 50 nm diameter, permitting bidirectional translocation at high speed. To achieve this, the NPC cooperates with soluble factors, the nuclear transport receptors, which shuttle between nuclear contents and cytoplasm. Here, we provide a short introduction to nucleocytoplasmic transport by describing first the structure and composition of the nuclear pore complex. Then, mechanisms of nucleocytoplasmic transport are discussed. Finally, the still essentially unresolved mechanisms by which nuclear transport receptors and transport complexes are translocated through the nuclear pore complex are considered, and a novel translocation model is suggested.

Key Words

Nuclear envelope nuclear pore complex nuclear transport receptors nucleocytoplasmic transport nucleoporins 


  1. 1.
    Callan, H. G., Randall, J. T. and Tomlin, S. G. (1949) An electron microscope study of the nuclear membrane. Nature 163, 280.PubMedCrossRefGoogle Scholar
  2. 2.
    Hutchison, C. J. (2002) Lamins: building blocks or regulators of gene expression? Nat. Rev. Mol. Cell Biol. 3, 848–858.PubMedCrossRefGoogle Scholar
  3. 3.
    Kau, T. R., Way, J. C. and Silver, P. A. (2004) Nuclear transport and cancer: from mechanism to intervention. Nat. Rev. Cancer 4, 106–117.PubMedCrossRefGoogle Scholar
  4. 4.
    Smith, J. M. and Koopman, P. A. (2004) The ins and outs of transcriptional control: nucleocytoplasmic shuttling in development and disease. Trends Genet. 20, 4–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Mounkes, L., Kozlov, S., Burke, B. and Stewart, C. L. (2003) The laminopathies: nuclear structure meets disease. Curr. Op. Genet. Dev. 13, 223–230.PubMedCrossRefGoogle Scholar
  6. 6.
    Cronshaw, J. M. and Matunis, M. J. (2004) The nuclear pore complex: disease associations and functional correlations. Trends Endocrinol. Metabol. 15, 34–39.CrossRefGoogle Scholar
  7. 7.
    Gorlich, D. and Mattaj, I. W. (1996) Protein kinesis-Nucleocytoplasmic transport. Science 271, 1513–1518.PubMedCrossRefGoogle Scholar
  8. 8.
    Macara, I. G. (2001) Transport into and out of the nucleus. Microbiol. Mol. Biol. Rev. 65, 570–594.PubMedCrossRefGoogle Scholar
  9. 9.
    Weis, K. (2003) Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle. Cell 112, 441–451.PubMedCrossRefGoogle Scholar
  10. 10.
    Bednenko, J., Cingolani, G. and Gerace, L. (2003) Nucleocytoplasmic transport: navigating the channel. Traffic 4, 127–135.PubMedCrossRefGoogle Scholar
  11. 11.
    Fahrenkrog, B. and Aebi, U. (2003) The nuclear pore complex: Nucleocytoplasmic transport and beyond. Nat. Rev. Mol. Cell Biol. 4, 757–766.PubMedGoogle Scholar
  12. 12.
    Rout, M. P., Aitchison, J. D., Magnasco, M. O. and Chait, B. T. (2003) Virtual gating and nuclear transport: the hole picture. Trends Cell Biol. 13, 622–628.PubMedCrossRefGoogle Scholar
  13. 13.
    Cullen, B. R. (2003) Nuclear RNA export. J. Cell Sci. 116, 587–597.PubMedCrossRefGoogle Scholar
  14. 14.
    Fried, H. and Kutay, U. (2003) Nucleocytoplasmic transport: taking an inventory. Cell. Mol. Life Sci. 60, 1659–1688.PubMedCrossRefGoogle Scholar
  15. 15.
    Suntharalingam, M. and Wente, S. R. (2003) Peering through the pore: Nuclear pore complex structure, assembly, and function. Dev. Cell 4, 775–789.PubMedCrossRefGoogle Scholar
  16. 16.
    Peters, R. (2003) Optical single transporter recording: Transport kinetics in microarrays of membrane patches. Annu. Rev. Biophys. Biomol. Struct. 32, 47–67.PubMedCrossRefGoogle Scholar
  17. 17.
    Peters, R., Lang, I., Scholz, M., Schulz, B. and Kayne, F. (1986) Fluorescence Microphotolysis to Measure Nucleocytoplasmic Transport In vivo and In vitro. Biochem. Sot: Trans. 14, 821–822.Google Scholar
  18. 18.
    Nelson, W. G., Pienta, K. J., Barrack, E. R. and Coffey, D. S. (1986) The Role of the Nuclear Matrix in the Organization and Function of DNA. Ann. Rev. Biophys. Biophysic. Chem. 15, 457–475.CrossRefGoogle Scholar
  19. 19.
    Pederson, T. (2000) Half a century of “the nuclear matrix”. Mol. Biol. Cell 11, 799–805.PubMedGoogle Scholar
  20. 20.
    Peters, R. (1986) Fluorescence Microphotolysis to Measure Nucleocytoplasmic Transport and Intracellular Mobility. Biochim. Biophys. Acta 864, 305–359.PubMedGoogle Scholar
  21. 21.
    Luby-Phelps, K. (2000) Cytoarchitecture and physical properties of cytoplasm: Volume, viscosity, diffusion, intracellular surface area. International Review of Cytology-A Survey of Cell Biology, Vol 192 192, 189–221.Google Scholar
  22. 22.
    Verkman, A. S. (2002) Solute and macromolecule diffusion in cellular aqueous compartments. Trends Biochem. Sci. 27, 27–33.PubMedCrossRefGoogle Scholar
  23. 23.
    Misteli, T. (2001) Nuclear structure-Protein dynamics: Implications for nuclear architecture and gene expression. Science 291, 843–847.PubMedCrossRefGoogle Scholar
  24. 24.
    Kues, T., Peters, R. and Kubitscheck, U. (2001) Visualization and tracking of single protein molecules in the cell nucleus. Biophys. J. 80, 2954–2967.PubMedCrossRefGoogle Scholar
  25. 25.
    Kues, T., Dickmanns, A., Luhrmann, R., Peters, R. and Kubitscheck, U. (2001) High intranuclear mobility and dynamic clustering of the splicing factor U1 snRNP observed by single particle tracking. Proc. Natl. Acad. Sci. USA 98, 12021–12026.PubMedCrossRefGoogle Scholar
  26. 26.
    Singh, O. P., Bjorkroth, B., Masich, S., Wieslander, L. and Daneholt, B. (1999) The intranuclear movement of Balbiani ring premessenger ribonucleoprotein particles. Exp. Cell Res. 251, 135–146.PubMedCrossRefGoogle Scholar
  27. 27.
    Politz, J. C. R., Tuft, R. A. and Pederson, T. (2003) Diffusion-based transport of nascent ribosomes in the nucleus. Mol. Biol. Cell 14, 4805–4812.PubMedCrossRefGoogle Scholar
  28. 28.
    Lamb, M. M. and Daneholt, B. (1979) Characterization of Active Transcription Units in Balbiani Rings of Chironomus Tentans. Cell 17, 835–848.PubMedCrossRefGoogle Scholar
  29. 29.
    Andersson, K., Bjorkroth, B. and Daneholt, B. (1980) The Insitu Structure of the Active 75-S Rna Genes in Balbiani Rings of Chironomus-Tentans. Exp. Cell Res. 130, 313–326.PubMedCrossRefGoogle Scholar
  30. 30.
    Skoglund, U., Andersson, K., Strandberg, B. and Daneholt, B. (1986) 3-Dimensional Structure of A Specific Pre-Messenger Rnp Particle Established by Electron-Microscope Tomography. Nature 319, 560–564.PubMedCrossRefGoogle Scholar
  31. 31.
    Mehlin, H., Daneholt, B. and Skoglund, U. (1992) Translocation of a Specific Premessenger Ribonucleoprotein Particle Through the Nuclear-Pore Studied with Electron-Microscope Tomography. Cell 69, 605–613.PubMedCrossRefGoogle Scholar
  32. 32.
    Franke, W. W. and Scheer, U. (1974) Structures and functions of the nuclear envelope. Cell Nucleus 1, 219–347.Google Scholar
  33. 33.
    Doring, V. and Stick, R. (1990) Gene Structure of Nuclear Lamin-Liii of Xenopus-Laevis-A Model for the Evolution of If Proteins from A Lamin-Like Ancestor. EMBO J. 9, 4073–4081.PubMedGoogle Scholar
  34. 34.
    Aebi, U., Cohn, J., Buhle, L. and Gerace, L. (1986) The Nuclear Lamina Is A Meshwork of Intermediate-Type Filaments. Nature 323, 560–564.PubMedCrossRefGoogle Scholar
  35. 35.
    Smythe, C, Jenkins, H. E. and Hutchison, C. J. (2000) Incorporation of the nuclear pore basket protein Nup 153 into nuclear pore structures is dependent upon lamina assembly: evidence from cell-free extracts of Xenopus eggs. EMBO J. 19, 3918–3931.PubMedCrossRefGoogle Scholar
  36. 36.
    Senior, A. and Gerace, L. (1988) Integral Membrane-Proteins Specific to the Inner Nuclear-Membrane and Associated with the Nuclear Lamina. J. Cell Biol. 107, 2029–2036.PubMedCrossRefGoogle Scholar
  37. 37.
    Jagatheesan, G., Thanumalayan, S., Muralikrishna, B., Rangaraj, N., Karande, A. A. and Parnaik, V. K. (1999) Colocalization of intranuclear lamin foci with RNA splicing factors. J. Cell Sci. 112, 4651–4661.PubMedGoogle Scholar
  38. 38.
    Stick, R. and Hausen, P. (1985) Changes in the Nuclear Lamina Composition During Early Development of Xenopus-Laevis. Cell 41, 191–200.PubMedCrossRefGoogle Scholar
  39. 39.
    Maul, G. G. (1977) The nuclear and cytoplasmic pore complex: Structure, dynamics, distribution, and evolution. Int. Rev. Cytol. Suppl. 6, 76–187.Google Scholar
  40. 40.
    Akey, C. W. (1989) Interactions and Structure of the Nuclear-Pore Complex Revealed by Cryo-Electron Microscopy. J. Cell Biol. 109, 955–970.PubMedCrossRefGoogle Scholar
  41. 41.
    Goldberg, M. W. and Allen, T. D. (1993) The Nuclear-Pore Complex-3-Dimensional Surface-Structure Revealed by Field-Emission, In-Lens Scanning Electron-Microscopy, with Underlying Structure Uncovered by Proteolysis. J. Cell Sci. 106, 261–274.PubMedGoogle Scholar
  42. 42.
    Allen, T. D., Cronshaw, J. M., Bagley, S., Kiseleva, E. and Goldberg, M. W. (2000) The nuclear pore complex: mediator of translocation between nucleus and cytoplasm. J. Cell Sci. 113, 1651–1659.PubMedGoogle Scholar
  43. 43.
    Scheer, U., Dabauvalle, M. C, Merkert, H. and Benavente, R. (1988) The nuclear envelope and the organization of the pore complex. Cell Biol. Int. Rep. 12, 669–689.PubMedCrossRefGoogle Scholar
  44. 44.
    Unwin, P. N. T. and Milligan, R. A. (1982) A Large Particle Associated with the Perimeter of the Nuclear-Pore Complex. J. Cell Biol. 93, 63–75.PubMedCrossRefGoogle Scholar
  45. 45.
    Akey, C. W. and Radermacher, M. (1993) Architecture of the Xenopus Nuclear Pore Complex Revealed by 3-Dimensional Cryoelectron Microscopy. J. Cell Biol. 122, 1–19.PubMedCrossRefGoogle Scholar
  46. 46.
    Stoffler, D., Feja, B., Fahrenkrog, B., Walz, J., Typke, D. and Aebi, U. (2003) Cryoelectron tomography provides novel insights into nuclear pore architecture: Implications for nucleocytoplasmic transport. J. Mol. Biol. 328, 119–130.PubMedCrossRefGoogle Scholar
  47. 47.
    Akey, C. W. (1990) Visualization of Transport-Related Configurations of the Nuclear-Pore Transporter. Biophys. J. 58, 341–355.PubMedCrossRefGoogle Scholar
  48. 48.
    Kiseleva, E., Goldberg, M. W., Allen, T. D. and Akey, C. W. (1998) Active nuclear pore complexes in Chironomus: visualization of transporter configurations related to mRNP export. J. Cell Sci. 111, 223–236.PubMedGoogle Scholar
  49. 49.
    Beck, M., Forster, F., Ecke, M., et al. (2004) Nuclear pore complex structure and dynamics revealed by cryoelectron tomography. Science 306, 1387–1390.PubMedCrossRefGoogle Scholar
  50. 50.
    Rout, M. P. and Blobel, G. (1993) Isolation of the Yeast Nuclear-Pore Complex. J. Cell Biol. 123, 771–783.PubMedCrossRefGoogle Scholar
  51. 51.
    Miller, B. R., Powers, M., Park, M., Fischer, W. and Forbes, D. J. (2000) Identification of a new vertebrate nucleoporin, Nup 188, with the use of a novel organelle trap assay. Mol. Biol. Cell 11, 3381–3396.PubMedGoogle Scholar
  52. 52.
    Rout, M. P., Aitchison, J. D., Suprapto, A., Hjertaas, K., Zhao, Y. M. and Chait, B. T. (2000) The yeast nuclear pore complex: Composition, architecture, and transport mechanism. J. Cell Biol. 148, 635–651.PubMedCrossRefGoogle Scholar
  53. 53.
    Cronshaw, J. A., Krutchinsky, A. N., Zhang, W. Z., Chait, B. T. and Matunis, M. J. (2002) Proteomic analysis of the mammalian nuclear pore complex. J. Cell Biol. 158, 915–927.PubMedCrossRefGoogle Scholar
  54. 54.
    Yang, Q., Rout, M. P. and Akey, C. W. (1998) Three-dimensional architecture of the isolated yeast nuclear pore complex: Functional and evolutionary implications. Mol. Cell 1, 223–234.PubMedCrossRefGoogle Scholar
  55. 55.
    Reichelt, R., Holzenburg, A., Buhle, E. L., Jarnik, M, Engel, A. and Aebi, U. (1990) Correlation Between Structure and Mass-Distribution of the Nuclear-Pore Complex and of Distinct Pore Complex Components. J. Cell Biol. 110, 883–894.PubMedCrossRefGoogle Scholar
  56. 56.
    Strawn, L. A., Shen, T. X., Shulga, N., Goldfarb, D. S. and Wente, S. R. (2004) Minimal nuclear pore complexes define FG repeat domains essential for transport. Nature Cell Biol. 6, 197–206.PubMedCrossRefGoogle Scholar
  57. 57.
    Denning, D. P., Patel, S. S., Uversky, V., Fink, A. L. and Rexach, M. (2003) Disorder in the nuclear pore complex: The FG repeat regions of nucleoporins are natively unfolded. Proc. Natl. Acad. Sci. USA 100, 2450–2455.PubMedCrossRefGoogle Scholar
  58. 58.
    Powers, M. A. and Dasso, M. (2004) Nuclear transport erupts on the slopes of Mount Etna. Nat. Cell Biol. 6, 82–86.PubMedCrossRefGoogle Scholar
  59. 59.
    Lutzmann, M., Kunze, R., Buerer, A., Aebi, U. and Hurt, E. (2002) Modular self-assembly of a Y-shaped multiprotein complex from seven nucleoporins. EMBOJ. 21, 387–397.CrossRefGoogle Scholar
  60. 60.
    Krull, S., Thyberg, J., Bjorkroth, B., Rackwitz, H. R. and Cordes, V. C. (2004) Nucleoporins as components of the nuclear pore complex core structure and Tpr as the architectural element of the nuclear basket. Mol. Biol. Cell 15, 4261–4277.PubMedCrossRefGoogle Scholar
  61. 61.
    Fahrenkrog, B., Maco, B., Fager, A. M., et al. (2002) Domain-specific antibodies reveal multiple-site topology of Nup 153 within the nuclear pore complex. J. Struct. Biol. 140, 254–267.PubMedCrossRefGoogle Scholar
  62. 62.
    Devos, D., Dokudovskaya, S., Alber, F., et al. (2004) Components of coated vesicles and nuclear pore complexes share a common molecular architecture. PLoS Biol. 2, e380.PubMedCrossRefGoogle Scholar
  63. 63.
    Paine, P. L., Moore, L. C. and Horowitz, S. B. (1975) Nuclear envelope permeability. Nature 254, 109–114.PubMedCrossRefGoogle Scholar
  64. 64.
    Pappenheimer, J. R., Renkin, E. M. and Borrero, L. M. (1951) Filtration, Diffusion and Molecular Sieving Through Peripheral Capillary Membranes A Contribution to the Pore Theory of Capillary Permeability. Am. J. Physiol. 167, 13–46.PubMedGoogle Scholar
  65. 65.
    Renkin, E. M. and Curry, F. E. (1979) Transport of water and solutes across endothelium. In Transport Organs (Giebisch, G., ed), Springer-Verlag, Berlin, pp. 1–45.Google Scholar
  66. 66.
    Keminer, O., Siebrasse, J. P., Zerf, K. and Peters, R. (1999) Optical recording of signalmediated protein transport through single nuclear pore complexes. Proc. Natl. Acad. Sci. USA 96, 11,842–11,847.PubMedCrossRefGoogle Scholar
  67. 67.
    Ribbeck, K. and Gorlich, D. (2001) Kinetic analysis of translocation through nuclear pore complexes. EMBO J. 20, 1320–1330.PubMedCrossRefGoogle Scholar
  68. 68.
    Siebrasse, J. P. and Peters, R. (2002) Rapid translocation of NTF2 through the nuclear pore of isolated nuclei and nuclear envelopes. EMBO Reports 3, 887–892.PubMedCrossRefGoogle Scholar
  69. 69.
    Kalderon, D., Richardson, W. D., Markham, A. F. and Smith, A. E. (1984) Sequence requirements for nuclear location of simian virus-40 large-T-antigen. Nature 311, 33–38.PubMedCrossRefGoogle Scholar
  70. 70.
    Dingwall, C, Robbins, J., Dilworth, S. M., Roberts, B. and Richardson, W. D. (1988) The Nucleoplasmin nuclear location sequence is larger and more complex than that of Sv40 large T-antigen. J. Cell Biol, 107, 841–849.PubMedCrossRefGoogle Scholar
  71. 71.
    Wen, W., Meinkoth, J. L., Tsien, R. Y. and Taylor, S. S. (1995) Identification of a signal for rapid export of proteins from the nucleus. Mol. Biol. Cell 6, 471.Google Scholar
  72. 72.
    Fischer, U., Huber, J., Boelens, W. C, Mattaj, I. W. and Luhrmann, R. (1995) The Hiv-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 82, 475–483.PubMedCrossRefGoogle Scholar
  73. 73.
    Michael, W. M., Choi, M. Y. and Dreyfuss, G. (1995) A nuclear export signal in hnRNP al-a signal-mediated, temperature-dependent nuclear-protein export pathway. Cell 83, 415–422.PubMedCrossRefGoogle Scholar
  74. 74.
    Nair, R., Carter, P. and Rost, B. (2003) NLSdb: database of nuclear localization signals. Nucleic Acids Res. 31, 397–399.PubMedCrossRefGoogle Scholar
  75. 75.
    Gorlich, D. and Kutay, U. (1999) Transport between the cell nucleus and the cytoplasm. Annu. Rev. Cell Dev. Biol. 15, 607–660.PubMedCrossRefGoogle Scholar
  76. 76.
    Chook, Y. M. and Blobel, G. (2001) Karyopherins and nuclear import. Curr. Opin. Struct. Biol. 11, 703–715.PubMedCrossRefGoogle Scholar
  77. 77.
    Conti, E. and Izaurralde, E. (2001) Nucleocytoplasmic transport enters the atomic age. Curr. Opin. Cell Biol. 13, 310–319.PubMedCrossRefGoogle Scholar
  78. 78.
    Andrade, M. A. and Bork, P. (1995) Heat repeats in the Huntingtons-disease protein. Nat. Genet. 11, 115–116.PubMedCrossRefGoogle Scholar
  79. 79.
    Fukuhara, N., Fernandez, E., Ebert, J., Conti, E. and Svergun, D. (2004) Conformational variability of nucleo-cytoplasmic transport factors. J. Biol. Chem. 279, 2176–2181.PubMedCrossRefGoogle Scholar
  80. 80.
    Fornerod, M., Ohno, M., Yoshida, M. and Mattaj, I. W. (1997) CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 90, 1051–1060.PubMedCrossRefGoogle Scholar
  81. 81.
    Vetter, I. R. and Wittinghofer, A. (2001) Signal transduction—The guanine nucleotidebinding switch in three dimensions. Science 294, 1299–1304.PubMedCrossRefGoogle Scholar
  82. 82.
    Matunis, M. J., Wu, J. A. and Blobel, G. (1998) SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAPl, to the nuclear pore complex. J. Cell Biol. 140, 499–509.PubMedCrossRefGoogle Scholar
  83. 83.
    Gorlich, D., Pante, N., Kutay, U., Aebi, U. and Bischoff, F. R. (1996) Identification of different roles for RanGDP and RanGTP in nuclear protein import. EMBO J. 15, 55845594.Google Scholar
  84. 84.
    Kalab, P., Weis, K. and Heald, R. (2002) Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science 295, 2452–2456.PubMedCrossRefGoogle Scholar
  85. 85.
    Reed, R. and Hurt, E. (2002) A conserved rnRNA export machinery coupled to pre-mRNA splicing. Cell 108, 523–531.PubMedCrossRefGoogle Scholar
  86. 86.
    Vinciguerra, P. and Stutz, F. (2004) MRNA export: an assembly line from genes to nuclear pores. Curr. Opin. Cell Biol. 16, 285–292.PubMedCrossRefGoogle Scholar
  87. 87.
    Dreyfuss, G., Kim, V. N. and Kataoka, N. (2002) Messenger-RNA-binding proteins and the messages they carry. Nat. Rev. Mol. Cell Biol. 3, 195–205.PubMedCrossRefGoogle Scholar
  88. 88.
    Le Hir, H., Izaurralde, E., Maquat, L. E. and Moore, M. J. (2000) The spliceosome deposits multiple proteins 20–24 nucleotides upstream of mRNA exon-exon junctions. EMBO J. 19, 6860–6869.PubMedCrossRefGoogle Scholar
  89. 89.
    Kataoka, N., Yong, J., Kim, V. N., et al. (2000) Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm. Mol. Cell 6, 673–682.PubMedCrossRefGoogle Scholar
  90. 90.
    Gilbert, W. and Guthrie, C. (2004) The Glc7p nuclear phosphatase promotes mRNA export by facilitating association of Mex67p with mRNA. Mol. Cell 13, 201–212.PubMedCrossRefGoogle Scholar
  91. 91.
    Izaurralde, E. (2004) Directing mRNA export. Nature Struct. Mol. Biol. 11, 210–212.CrossRefGoogle Scholar
  92. 92.
    Strasser, K. and Hurt, E. (2000) Yralp, a conserved nuclear RNA-binding protein, interacts directly with Mex67p and is required for mRNA export. EMBO J. 19, 410–420.PubMedCrossRefGoogle Scholar
  93. 93.
    Kang, Y. B. and Cullen, B. R. (1999) The human Tap protein is a nuclear mRNA export factor that contains novel RNA-binding and nucleocytoplasmic transport sequences. Genes Develop. 13, 1126–1139.PubMedCrossRefGoogle Scholar
  94. 94.
    Rodriguez-Navarro, S., Fischer, T., Luo, M. J., et al. (2004) Susl, a functional component of the SAGA histone acetylase complex and the nuclear pore-associated mRNA export machinery. Cell 116, 75–86.PubMedCrossRefGoogle Scholar
  95. 95.
    Erkmann, J. A. and Kutay, U. (2004) Nuclear export of mRNA: from the site of transcription to the cytoplasm. Exp. Cell Res. 296, 12–20.PubMedCrossRefGoogle Scholar
  96. 96.
    Katahira, J., Strasser, K., Podtelejnikov, A., Mann, M., Jung, J. U. and Hurt, E. (1999) The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human. EMBO J. 18, 2593–2609.PubMedCrossRefGoogle Scholar
  97. 97.
    Herold, A., Suyama, M., Rodrigues, J. P., et al. (2000) TAP (NXF1) belongs to a multigene family of putative RNA export factors with a conserved modular architecture. Mol. Cell. Biol. 20, 8996–9008.PubMedCrossRefGoogle Scholar
  98. 98.
    Black, B. E., Levesque, L., Holaska, J. M., Wood, T. C. and Paschal, B. M. (1999) Identification of an NTF2-related factor that binds Ran-GTP and regulates nuclear protein export. Mol. Cell. Biol. 19, 8616–8624.PubMedGoogle Scholar
  99. 99.
    Fribourg, S. and Conti, E. (2003) Structural similarity in the absence of sequence homology of the messenger RNA export factors Mtr2 and p15. EMBO Rep. 4, 699–703.PubMedCrossRefGoogle Scholar
  100. 100.
    Liker, E., Fernandez, E., Izaurralde, E. and Conti, E. (2000) The structure of the mRNA export factor TAP reveals a cis arrangement of a non-canonical RNP domain and an LRR domain. EMBO J. 19, 5587–5598.PubMedCrossRefGoogle Scholar
  101. 101.
    Ho, D. N., Coburn, G. A., Kang, Y. B., Cullen, B. R. and Georgiadis, M. M. (2002) The crystal structure and mutational analysis of a novel RNA-binding domain found in the human Tap nuclear mRNA export factor. Proc. Nad. head. Sci. USA 99, 1888–1893.CrossRefGoogle Scholar
  102. 102.
    Fribourg, S., Braun, I. C., Izaurralde, E. and Conti, E. (2001) Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like domain of the TAP/p15 mRNA nuclear export factor. Mol. Cell 8, 645–656.PubMedCrossRefGoogle Scholar
  103. 103.
    Grant, R. P., Hurt, E., Neuhaus, D. and Stewart, M. (2002) Structure of the C-terminal FG-nucleoporin binding domain of Tap/NXFl. Nat. Struct. Biol. 9, 247–251.PubMedCrossRefGoogle Scholar
  104. 104.
    Stutz, F. and Izaurralde, E. (2003) The interplay of nuclear mRNP assembly, mRNA surveillance and export. Trends Cell Biol. 13, 319–327.PubMedCrossRefGoogle Scholar
  105. 105.
    Gruter, P., Tabernero, C, von Kobbe, C, et al. (1998) TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol. Cell 1, 649–659.PubMedCrossRefGoogle Scholar
  106. 106.
    Bullock, T. L., Clarkson, W. D., Kent, H. M. and Stewart, M. (1996) The 1.6 angstrom resolution crystal structure of nuclear transport factor 2 (NTF2) J. Mol. Biol. 260, 422–431.PubMedCrossRefGoogle Scholar
  107. 107.
    Snay-Hodge, C. A., Colot, H. V., Goldstein, A. L. and Cole, C. N. (1998) Dbp5p/Rat8p is a yeast nuclear pore-associated DEAD-box protein essential for RNA export. EMBO J. 17, 2663–2676.PubMedCrossRefGoogle Scholar
  108. 108.
    Maquat, L. E. (2004) Nonsense-mediated mRNA decay: Splicing, translation and mRNP dynamics. Nat. Rev. Mol. Cell Biol. 5, 89–99.PubMedCrossRefGoogle Scholar
  109. 109.
    Rexach, M. and Blobel, G. (1995) Protein import into nuclei: association and dissociation reactions involving transport substrate, transport factors, and nucleoporins. Cell 83, 683–692.PubMedCrossRefGoogle Scholar
  110. 110.
    Feldherr, C. M. and Akin, D. (1997) The location of the transport gate in the nuclear pore complex. J. Cell Sci. 110, 3065–3070.PubMedGoogle Scholar
  111. 111.
    Bayliss, R., Corbett, A. H. and Stewart, M. (2000) The molecular mechanism of transport of macromolecules through nuclear pore complexes. Traffic 1, 448–456.PubMedCrossRefGoogle Scholar
  112. 112.
    Ben-Efraim, I. and Gerace, L. (2001) Gradient of increasing affinity of importin beta for nucleoporins along the pathway of nuclear import. J. Cell Biol. 152, 411–417.PubMedCrossRefGoogle Scholar
  113. 113.
    Bickel, T. and Bruinsma, R. (2002) The nuclear pore complex mystery and anomalous diffusion in reversible gels. Biophys. J. 83, 3079–3087.PubMedCrossRefGoogle Scholar
  114. 114.
    Kustanovich, T. and Rabin, Y. (2004) Metastable network model of protein transport through nuclear pores. Biophys. J. 86, 2008–2016.PubMedCrossRefGoogle Scholar
  115. 115.
    Fahrenkrog, B., Koser, J. and Aebi, U. (2004) The nuclear pore complex: a jack of all trades? Trends Biochem. Sci. 29, 175–182.PubMedCrossRefGoogle Scholar
  116. 116.
    Peters, R. (2005) Translocation through the nuclear pore complex: Selectivity and speed by reduction-of-dimensionality. Traffic 6, 421–427.PubMedCrossRefGoogle Scholar
  117. 117.
    Shulga, N. and Goldfarb, D. S. (2003) Binding dynamics of structural nucleoporins govern nuclear pore complex permeability and may mediate channel gating. Mol. Cell. Biol. 23, 534–542.PubMedCrossRefGoogle Scholar
  118. 118.
    Grote, M., Kubitscheck, U., Reichelt, R. and Peters, R. (1995) Mapping of Nucleoporins to the Center of the Nuclear-Pore Complex by Postembedding Immunogold Electron-Microscopy. J. Cell Sci. 108, 2963–2972.PubMedGoogle Scholar
  119. 119.
    Kubitscheck, U., Griinwald, D., Hoekstra, A., et al. (2005) Nuclear transport of single molecules: Dwell times at the nuclear pore complex. J. Cell Biol. 168, 233–243.PubMedCrossRefGoogle Scholar
  120. 120.
    Stewart, M., Baker, R. P., Bayliss, R., et al. (2001) Molecular mechanism of translocation through nuclear pore complexes during nuclear protein import. FEBS Lett. 498, 145–149.PubMedCrossRefGoogle Scholar
  121. 121.
    Zeitler, B. and Weis, K. (2004) The FG-repeat asymmetry of the nuclear pore complex is dispensable for bulk nucleocytoplasmic transport in vivo. J. Cell Biol. 167, 583–590.PubMedCrossRefGoogle Scholar
  122. 122.
    Ribbeck, K. and Gorlich, D. (2002) The permeability barrier of nuclear pore complexes appears to operate via hydrophobic exclusion. EMBO J. 21, 2664–2671.PubMedCrossRefGoogle Scholar
  123. 123.
    Berg, O. G. and von Hippel, P. H. (1985) Diffusion-controlled macromolecular interactions. Anna. Rev. Biophys. Biophys. Chem. 14, 131–160.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Reiner Peters
    • 1
  1. 1.Institute of Medical Physics and Biophysics and Center for Nanotechnology (CeNTech)University of MünsterMünsterGermany

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