Nuclear‐Cytoplasmic Transport

Allison Lange, Emory University School of Medicine, Atlanta, Georgia, USA
Anita H Corbett, Emory University School of Medicine, Atlanta, Georgia, USA

Published online: September 2009

DOI: 10.1002/9780470015902.a0001351.pub2

In eukaryotic cells, the genomic deoxyribonucleic acid (DNA) in the nucleus is separated from the translational machinery in the cytoplasm by the nuclear envelope. Transport of macromolecules such as proteins and ribonucleic acid (RNA) across this membrane is essential for cellular function and requires active nuclear–cytoplasmic transport systems. These systems consist of soluble transport receptors, which recognize and bind cargo in one compartment, mediate transport through nuclear pore complexes embedded in the nuclear envelope and deliver cargo in the target compartment. Disruption of this highly regulated process results in abnormal cell function and is linked to human disease etiology. Understanding the contribution of nuclear protein and RNA transport to cellular organization is one of the major challenges in cell biology.

Key Concepts

  • Transport into and out of the nucleus occurs through nuclear pore complexes (NPCs), which are large proteinaceous channels that perforate the nuclear membrane.
  • Proteins destined for import into the nucleus contain a nuclear localization signal (NLS) and proteins destined for export from the nucleus contain a nuclear export signal (NES), each of which targets them for transport.
  • Soluble transport receptors called importins and exportins or karyopherins recognize and bind macromolecular cargos and facilitate transport through the nuclear pore.
  • The asymmetric distribution of RanGDP in the cytoplasm and RanGTP in the nucleus controls the directionality of nuclear transport.
  • Nuclear protein import can be regulated through inter- or intramolecular occlusion of the NLS or NES; posttranslation modification of the targeting signal; compartmental sequestration of the cargo protein or altering properties of the nuclear transport machinery including receptors and nuclear pores.
  • Many classes of RNA are transported via Ran-regulated, karyopherin-dependent pathways.
  • Messenger ribonucleic acid (mRNA) export is highly coupled to mRNA processing and is mediated by distinct receptors.
  • Mutations in nuclear targeting signals and nuclear transport receptors have been linked to several human diseases.

Keywords: nuclear transport; importin; karyopherin; nuclear pore complex; nucleocytoplasmic trafficking

Figure 1. The nuclear pore complex. Cartoon representation of a cross-section of the nuclear pore, which is comprised of a cylindrical channel embedded in the nuclear membrane, filaments extending into the cytoplasm and a basket structure reaching into the nucleus (Alber et al., 2007).
Figure 2. The Ran gradient. The proteins that regulate the Ran cycle are asymmetrically distributed in the cell, with the Ran GTPase activating protein (RanGAP) in the cytoplasm and the Ran guanine nucleotide exchange factor (RanGEF) in the nucleus (Becker et al., 1995; Bischoff and Ponstingl, 1991). This distribution results in a predominantly cytoplasmic localization for RanGDP and a predominantly nuclear localization for RanGTP (Kalab et al., 2002).
Figure 3. The classical nuclear import cycle. In the cytoplasm, cargo containing a cNLS is bound by the heterodimeric import receptor, importin /importin (Görlich et al., 1995). Importin recognizes the cNLS and importin mediates interactions with the nuclear pore during translocation. Once inside the nucleus, RanGTP-binding causes a conformational change in importin , which releases the IBB region of importin . This auto-inhibitory domain, together with Nup2 and Cse1, facilitates cNLS dissociation and delivery of the cNLS-cargo in the nucleus (Gilchrist et al., 2002; Harreman et al., 2003). Finally, importin is recycled back to the cytoplasm by the export receptor, Cse1, in complex with RanGTP (Kutay et al., 1997).
Figure 4. Karyopherin crystal structures. A, importin lacking the IBB domain bound to two SV40 NLS peptides (Protein Data Bank entry 1BK6) (Conti et al., 1998). Importin (amino acids 88–530) is shown in orange. The SV40 peptides are shown in yellow. B, the classical -karyopherin, importin , bound to two different binding partners. Importin is shown in blue and the binding partner is shown in yellow. On the left, importin is bound on a convex face by the FG-repeats of the nucleoporin, Nup1. On the right, importin is bound on a concave surface by the NLS of parathyroid hormone-related protein, PTHrP. (Protein Data Bank entries 2BPT and 1M5N) (Cingolani et al., 2002; Liu and Stewart, 2005).
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Related Sub-Topics:

Cell Membranes | Cellular Transport | Cell Compartments and Cellular Organelles | Membrane Proteins | Cell Motility and Transport | Molecular Transport
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Article Title: Nuclear‐Cytoplasmic Transport
 
How to Cite close
Lange, Allison, and Corbett, Anita H(Sep 2009) Nuclear‐Cytoplasmic Transport. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001351.pub2]