The Nuclear Pore Complex and Nuclear Transport


The nuclear pore complex (NPC) is an essential gateway between the cell nucleus and the cytoplasm. The NPC is formed by multiple copies of ∼30 different proteins called nucleoporins, which can be divided into scaffold, membrane‐anchored and barrier components. Thousands of phenylalanine‐glycine (FG) repeats, found in barrier nucleoporins, interact to form the selective permeability barrier of the NPC channel. Shuttling nuclear transport receptors are able to interact with these FG repeats and mediate the passage of large macromolecular cargoes through the barrier. Combinations of shuttling receptors, their adaptors and localisation signals in cargo molecules define a wide array of nuclear import and export pathways. Recent research has pointed to some dynamic features in NPC components, as well as a number of nucleoporin‐related human diseases which are characterised by highly cell‐type‐specific phenotypes.

Key Concepts

  • The nuclear pore complex (NPC) is a massive and elaborate structure formed by multiple copies of ∼30 different nucleoporins.
  • The selective permeability barrier of the NPC is formed by hydrophobic interactions among FG repeats found in a large group of nucleoporins.
  • Ions and small molecules are able to passively diffuse through the aqueous central channel of the NPC.
  • Macromolecules transported through the NPC must contain specific targeting signals for nuclear import and nuclear export.
  • Targeting signals are recognised by shuttling transport receptors which mediate the passage through the NPC channel by interacting with FG repeats.
  • A small number of inherited diseases have been linked to mutations in human nucleoporins and are characterised by cell‐type‐specific phenotypes.

Keywords: nuclear pore complex; nucleoporins; nuclear envelope; nuclear pore scaffold; nuclear transport; FG repeats; karyopherins

Figure 1. (a, b) Structure and composition of the nuclear pore complex. A schematic cross section of the NPC is shown on the right, emphasising the major structural modules (in different shades of blue) and the rotational symmetry of the structure. Membranes are shown in yellow. The whole structure is tightly embedded within the curved pore‐membrane domain connecting the inner and outer nuclear membranes. On the left: a diagram showing the division of vertebrate nucleoporins into major subcomplexes and their approximate positions within the structure. Note that the exact contact sites among subcomplexes and other features of this supramolecular assembly are still being investigated and debated.
Figure 2. Direct surface imaging of NPCs in a human cell nucleus. Primary fibroblasts were subjected to hypotonic treatment in order to expose their nuclei and obtain high‐resolution images by scanning electron microscopy. See Fichtman et al. () for further details of this procedure. Three successive magnifications are shown; starting with a whole intact nucleus and finally focusing on an area containing three individual NPCs. Smaller particles protruding from the outer nuclear membrane are thought to be ribosomes. The sample was coated with a thin layer of iridium in order to allow direct surface imaging in a scanning electron microscope. Partially collapsed cytoplasmic filaments are observed on the cytoplasmic facade of NPCs and some details of internal structures are seen through open pore channels.
Figure 3. The Y‐complex within the NPC scaffold. A three‐dimensional model showing the position of 16 copies of the human Nup107–160 subcomplex within the cytoplasmic ring of the NPC. The tomographic scaffold structure (top view, from the cytoplasmic side) shows general protein densities in grey, membranes in yellow and pairs of inner and outer copies of the Nup107–160 subcomplex in green and blue, respectively. The elongated Y‐shaped structure of a single subcomplex unit can be identified at the 6 o'clock position. Sixteen additional copies are similarly arranged within the nuclear ring, on the other side of the scaffold. Image was kindly provided by Martin Beck. See (Bui et al., 2013) for further details.


Adam SA, Marr RS and Gerace L (1990) Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors. Journal of Cell Biology 111: 807–816.

Antonin W, Franz C, Haselmann U, Antony C and Mattaj IW (2005) The integral membrane nucleoporin pom121 functionally links nuclear pore complex assembly and nuclear envelope formation. Molecular Cell 17: 83–92.

Basel‐Vanagaite L, Muncher L, Straussberg R, et al. (2006) Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis. Annals of Neurology 60: 214–222.

Beck M, Forster F, Ecke M, et al. (2004) Nuclear pore complex structure and dynamics revealed by cryoelectron tomography. Science 306: 1387–1390.

Beck M, Lucic V, Forster F, Baumeister W and Medalia O (2007) Snapshots of nuclear pore complexes in action captured by cryo‐electron tomography. Nature 449: 611–615.

Belgareh N, Rabut G, BAI SW, et al. (2001) An evolutionarily conserved NPC subcomplex, which redistributes in part to kinetochores in mammalian cells. Journal of Cell Biology 154: 1147–1160.

Brohawn SG, Partridge JR, Whittle JR and Schwartz TU (2009) The nuclear pore complex has entered the atomic age. Structure 17: 1156–1168.

Bui KH, von Appen A, Diguilio AL, et al. (2013) Integrated structural analysis of the human nuclear pore complex scaffold. Cell 155: 1233–1243.

Capelson M, Liang Y, Schulte R, et al. (2010) Chromatin‐bound nuclear pore components regulate gene expression in higher eukaryotes. Cell 140: 372–383.

Cronshaw JM, Krutchinsky AN, Zhang W, Chait BT and Matunis MJ (2002) Proteomic analysis of the mammalian nuclear pore complex. Journal of Cell Biology 158: 915–927.

Cronshaw JM and Matunis MJ (2003) The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome. Proceedings of the National Academy of Sciences of the United States of America 100: 5823–5827.

D'Angelo MA, Gomez‐Cavazos JS, Mei A, Lackner DH and Hetzer MW (2012) A change in nuclear pore complex composition regulates cell differentiation. Developmental Cell 22: 446–458.

Daneholt B (2001) Assembly and transport of a premessenger RNP particle. Proceedings of the National Academy of Sciences of the United States of America 98: 7012–7017.

Dimaano C and Ullman KS (2004) Nucleocytoplasmic transport: integrating mRNA production and turnover with export through the nuclear pore. Molecular and Cellular Biology 24: 3069–3076.

Fahrenkrog B, Koser J and Aebi U (2004) The nuclear pore complex: a jack of all trades? Trends in Biochemical Sciences 29: 175–182.

Fichtman B, Shaulov L and Harel A (2014) Imaging metazoan nuclear pore complexes by field emission scanning electron microscopy. Methods in Cell Biology 122: 41–58.

Frey S and Gorlich D (2007) A saturated FG‐repeat hydrogel can reproduce the permeability properties of nuclear pore complexes. Cell 130: 512–523.

Gerace L and Burke B (1988) Functional organization of the nuclear envelope. Annual Review of Cell Biology 4: 335–374.

Gorlich D, Dabrowski M, Bischoff FR, et al. (1997) A novel class of RanGTP binding proteins. Journal of Cell Biology 138: 65–80.

Gorlich D and Kutay U (1999) Transport between the cell nucleus and the cytoplasm. Annual Review of Cell and Developmental Biology 15: 607–660.

Gough SM, Slape CI and Aplan PD (2011) NUP98 gene fusions and hematopoietic malignancies: common themes and new biologic insights. Blood 118: 6247–6257.

Harel A, Orjalo AV, Vincent T, et al. (2003) Removal of a single pore subcomplex results in vertebrate nuclei devoid of nuclear pores. Molecular Cell 11: 853–864.

Hetzer MW and Wente SR (2009) Border control at the nucleus: biogenesis and organization of the nuclear membrane and pore complexes. Developmental Cell 17: 606–616.

Hinshaw JE, Carragher BO and Milligan RA (1992) Architecture and design of the nuclear pore complex. Cell 69: 1133–1141.

Hodge CA, Tran EJ, Noble KN, et al. (2011) The Dbp5 cycle at the nuclear pore complex during mRNA export I: dbp5 mutants with defects in RNA binding and ATP hydrolysis define key steps for Nup159 and Gle1. Genes and Development 25: 1052–1064.

Hoelz A, Debler EW and Blobel G (2011) The structure of the nuclear pore complex. Annual Review of Biochemistry 80: 613–643.

Hulsmann BB, Labokha AA and Gorlich D (2012) The permeability of reconstituted nuclear pores provides direct evidence for the selective phase model. Cell 150: 738–751.

Hurt EC (1988) A novel nucleoskeletal‐like protein located at the nuclear periphery is required for the life cycle of Saccharomyces cerevisiae. EMBO Journal 7: 4323–4334.

Jarnik M and Aebi U (1991) Toward a more complete 3‐D structure of the nuclear pore complex. Journal of Structural Biology 107: 291–308.

Kalverda B, Pickersgill H, Shloma VV and Fornerod M (2010) Nucleoporins directly stimulate expression of developmental and cell‐cycle genes inside the nucleoplasm. Cell 140: 360–371.

Kinoshita Y, Kalir T, Dottino P and Kohtz DS (2012) Nuclear distributions of NUP62 and NUP214 suggest architectural diversity and spatial patterning among nuclear pore complexes. PLoS One 7: e36137.

Lim RY, Fahrenkrog B, Koser J, et al. (2007) Nanomechanical basis of selective gating by the nuclear pore complex. Science 318: 640–643.

Maimon T and Medalia O (2010) Perspective on the metazoan nuclear pore complex. Nucleus 1: 383–386.

Makhnevych T, Lusk CP, Anderson AM, Aitchison JD and Wozniak RW (2003) Cell cycle regulated transport controlled by alterations in the nuclear pore complex. Cell 115: 813–823.

Mattaj IW and Englmeier L (1998) Nucleocytoplasmic transport: the soluble phase. Annual Review of Biochemistry 67: 265–306.

Ori A, Banterle N, Iskar M, et al. (2013) Cell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machines. Molecular Systems Biology 9: 648.

Pante N and Kann M (2002) Nuclear pore complex is able to transport macromolecules with diameters of about 39 nm. Molecular Biology of the Cell 13: 425–434.

Radu A, Moore MS and Blobel G (1995) The peptide repeat domain of nucleoporin Nup98 functions as a docking site in transport across the nuclear pore complex. Cell 81: 215–222.

Rasala BA, Orjalo AV, Shen Z, Briggs S and Forbes DJ (2006) ELYS is a dual nucleoporin/kinetochore protein required for nuclear pore assembly and proper cell division. Proceedings of the National Academy of Sciences of the United States of America 103: 17801–17806.

Rotem A, Gruber R, Shorer H, et al. (2009) Importin beta regulates the seeding of chromatin with initiation sites for nuclear pore assembly. Molecular Biology of the Cell 20: 4031–4042.

Rout MP, Aitchison JD, Suprapto A, et al. (2000) The yeast nuclear pore complex: composition, architecture, and transport mechanism. Journal of Cell Biology 148: 635–651.

Savas JN, Toyama BH, Xu T, Yates JR 3rd and Hetzer MW (2012) Extremely long‐lived nuclear pore proteins in the rat brain. Science 335: 942.

Schwartz TU (2005) Modularity within the architecture of the nuclear pore complex. Current Opinion in Structural Biology 15: 221–226.

Shaulov L, Gruber R, Cohen I and Harel A (2011) A dominant‐negative form of POM121 binds chromatin and disrupts the two separate modes of nuclear pore assembly. Journal of Cell Science 124: 3822–3834.

Stavru F, Hulsmann BB, Spang A, et al. (2006) NDC1: a crucial membrane‐integral nucleoporin of metazoan nuclear pore complexes. Journal of Cell Biology 173: 509–519.

Terry LJ, Shows EB and Wente SR (2007) Crossing the nuclear envelope: hierarchical regulation of nucleocytoplasmic transport. Science 318: 1412–1416.

Tran EJ and Wente SR (2006) Dynamic nuclear pore complexes: life on the edge. Cell 125: 1041–1053.

Tschochner H and Hurt E (2003) Pre‐ribosomes on the road from the nucleolus to the cytoplasm. Trends in Cell Biology 13: 255–263.

Weis K (2003) Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle. Cell 112: 441–451.

Zhang X, Chen S, Yoo S, et al. (2008) Mutation in nuclear pore component NUP155 leads to atrial fibrillation and early sudden cardiac death. Cell 135: 1017–1027.

Further Reading

Bilokapic S and Schwartz TU (2012) 3D ultrastructure of the nuclear pore complex. Current Opinion in Cell Biology 24: 86–91.

Fichtman B and Harel A (2014) Stress and aging at the nuclear gateway. Mechanisms of Ageing and Development 135: 24–32.

Fried H and Kutay U (2003) Nucleocytoplasmic transport: taking an inventory. Cellular and Molecular Life Sciences 60: 1659–1688.

Harel A and Forbes DJ (2004) Importin beta: conducting a much larger cellular symphony. Molecular Cell 16: 319–330.

Powers MA and Forbes DJ (2012) Nuclear transport: beginning to gel? Current Biology 22: R1006–R1009.

Weis K (2007) The nuclear pore complex: oily spaghetti or gummy bear? Cell 130: 405–407.

Wente SR and Rout MP (2010) The nuclear pore complex and nuclear transport. Cold Spring Harbor Perspectives in Biology 2: a000562.

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Zagairy, Fadia, Fichtman, Boris, and Harel, Amnon(Apr 2015) The Nuclear Pore Complex and Nuclear Transport. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0026034]