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The nuclear pore complex: nucleocytoplasmic transport and beyond

Nature Reviews Molecular Cell Biology volume 4, pages 757–766 (2003)Cite this article

Key Points

  • The nuclear pore complex (NPC) is the only known gateway between the cell nucleus and the cytoplasm. Its three-dimensional architecture has been determined from electron-microscopy studies, mainly of the nuclear envelopes of Xenopus laevis oocytes.

  • The central framework of the NPC has an eightfold rotational symmetry in the plane of the nuclear envelope and embraces the central pore of the NPC. The functional diameter of this central pore is ∼30–40 nm, which is close to its physical diameter of 45–50 nm.

  • Seen in projection, the central pore often seems obstructed by a central plug, which represents a composite of the distal ring of the NPC's nuclear basket and cargo caught in transit through the central pore.

  • The NPC is composed of about ∼30 different proteins called nucleoporins, some of which seem to be mobile within the NPC and are involved in cellular processes other than nucleocytoplasmic transport (for example, chromosome segregation and kinetochore integrity).

  • Translocation of a cargo–receptor complex through the NPC involves its interaction, through the receptor, with nucleoporins that have FG-repeat domains. FG repeats are highly flexible and rather mobile within the NPC, which increases the efficiency of nucleocytoplasmic transport of signal-bearing cargo.

  • Translocation of signal-bearing cargo through the NPC is a thermal-energy-driven stochastic event. It is turned into a net directed motion through the action of molecular switches such as Ran that — through the RanGTPase cycle — forms a RanGDP/RanGTP gradient between the cytoplasmic and nuclear periphery of the NPC.

Abstract

Over the past two years, it has become evident that there is an unexpected link between nuclear pore complex structure and dynamics, nucleocytoplasmic transport and chromosome segregation. In addition, a tomographic three-dimensional reconstruction of native nuclear pore complexes preserved in thick amorphous ice has unveiled a number of new structural features of this supramolecular machine. These data, together with some of the elementary physical principles that underlie nucleocytoplasmic transport, will be discussed in this review.

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Figure 1: Schematic representation of the three-dimensional nuclear pore complex consensus model.
Figure 2: Comparing native and detergent-extracted nuclear pore complexes.
Figure 3: Domain topography of the nucleoporin Nup153 in the nuclear pore complex.
Figure 4: Towards a more realistic nucleocytoplasmic transport model.
Figure 5: The common themes of molecular motors and G proteins.

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Acknowledgements

This work was supported by grants from the Swiss National Science Foundation (B.F.) and the Human Frontier Science Program (U.A.), and by funds provided by the Maurice E. Müller Foundation of Switzerland and the Kanton Basel-Stadt.

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  1. Maurice E. Müller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstr. 70, Basel, CH-4056, Switzerland

    Birthe Fahrenkrog & Ueli Aebi

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  1. Birthe Fahrenkrog
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Correspondence to Birthe Fahrenkrog.

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DATABASES

LocusLink

Nup98

Nup153

Nup214

Saccharomyces Genome Database

Kap60

Kap95

Mad1

Mad2

Mlp1

Nup2

NUP170

Swiss-Prot

MAD1

MAD2

NTF2

Nup50

Nup107

Nup133

Rae1

RanBP2

Tankyrase

TAP

TRF1

FURTHER INFORMATION

Ueli Aebi's laboratory

Biozentrum, University of Basel, Switzerland

Glossary

NEGATIVE STAIN

The deposit of heavy metal salts — for example, by using uranyl-acetate or uranyl-formate solutions — to increase the contrast of biological samples for electron microscopy.

FROZEN-HYDRATED

This term describes samples that are prepared for transmission electron microscopy using quick freezing to minimize the problem of ice-crystal formation. This method also prevents ice crystals forming during frozen storage without the need for dehydration and fixation of the sample.

TOMOGRAPHIC 3D RECONSTRUCTION

The three-dimensional reconstruction of an object from a series of projections. Two-dimensional projection images are recorded while tilting either the object or the illumination and detector around an axis.

AMORPHOUS ICE

Ice can exist in numerous forms depending on the temperature and pressure. At temperatures of about −160°C to −50°C, ice 'prefers' to stack with a four-sided symmetry (cubic ice). Ice formed by condensing water vapour at even lower temperatures is amorphous.

BALBIANI RING mRNP PARTICLES

Balbiani ring mRNP particles are giant puffs of polytene chromosomes in dipteran insects. They are most frequently studied in larval-salivary-gland cells of the midge Chironomous tentans.

NUCLEAR LOCALIZATION SIGNAL

A stretch of basic amino acids that is required for the nuclear import of a protein.

IMPORTIN-α

A transport adaptor that bridges the interaction between a nuclear-localization-signal-containing cargo and the transport receptor, importin-β.

IMPORTIN-β

A RanGTP-binding protein that bridges the interaction between the cargo and the nuclear pore complex.

QUICK-FREEZE/FREEZE-DRYING

A cryo preparation method that is used for samples that will be studied by transmission electron microscopy. Samples are fixed by plunging them into cryogens — such as, for example, liquid ethane or a mixture of propane and isopentane — that are cooled in liquid nitrogen. Under a vacuum, the specimen is then allowed to dry at −110°C to prevent rehydration.

TILT SERIES

When obtaining a tilt series for three-dimensional reconstruction, the specimen is typically tilted from −60° to +60° in 1.5° intervals. The images are then aligned in a tilt series and a tomogram is calculated from these data.

CRITICAL-POINT DRYING

A sample preparation method for scanning electron microscopy. The liquid in the sample is exchanged for a solvent, which bypasses the liquid to gas phase transition and thereby avoids artefacts due to surface tension.

FG REPEAT

A phenylalanine–glycine repeat motif that is found in the amino-acid sequence of many nucleoporins. It is required for the interaction of nucleoporins with transport receptors.

GLFG NUCLEAR BODIES

The nucleoporin Nup98 is localized to the nuclear pore complex and to intranuclear bodies, and it is the glycine–leucine–phenylalanine–glycine-repeat domain of Nup98 that targets it to these bodies, which are therefore referred to as GLFG bodies.

KINETOCHORE

A centromeric substructure that binds microtubules and directs the movement of chromosomes in mitosis.

BROWNIAN MOTION

The random thermal motion of particles that are suspended in a gas or liquid.

RHEOLOGY

Rheology is the science of the flow and deformation of materials and describes the interrelationship between force, deformation and time.

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Fahrenkrog, B., Aebi, U. The nuclear pore complex: nucleocytoplasmic transport and beyond. Nat Rev Mol Cell Biol 4, 757–766 (2003). https://doi.org/10.1038/nrm1230

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  • DOI: https://doi.org/10.1038/nrm1230

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