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Ran GTPASE Regulation of the CRM1-Dependent Export Pathway

  • Bryce M. Paschal
  • Catherine Dargemont

Abstract

Nuclear proteins that are not stably bound to intranuclear structures have the potential to be transported to the cytoplasm. Recent studies on proteins that undergo nuclear export led to the identification of cis-acting nuclear export signals or NES. These short sequence motifs are recognized by specific receptors, called karyopherins or exportins, which belong to a large family of proteins conserved through evolution. The NES, which in both cellular and viral proteins is enriched in hydrophobic amino acids including leucine, specifically interacts with the nuclear export receptor CRM1. The function of CRM1 is to mediate association with the nuclear pore complex and translocation of the NES protein to the cytoplasm. Binding of NES to CRM1 occurs in a Ran-GTP-dependent manner, but GTP hydrolysis is not required for this binding, or for translocation of the export complex through the NPC. CRM1 and Ran are sufficient to promote translocation of the cargo from the nucleoplasm to the cytoplasmic face of the nuclear pore complex, however, additional Ran·TP-binding proteins including the newly described NXT1 protein are also required to facilitate nuclear export. In the cytoplasm, dissociation of Ran from the export complex is triggered by the concerted action of different Ran regulatory proteins. These include the Ran GTPase Activating Protein, Ran Binding Proteins 1 and 2, and NXT1. Ran dissociation reverses the interactions between NES and CRM1, and CRM1 and the nuclear pore complex. Thus, disassembly of the nuclear export complex leads to the release of the NES-containing cargo in the cytoplasm and the recycling of CRM 1 back to the nucleus where it is available for a new round of transport. In this review, we describe what is known about the various steps in nuclear export of proteins and RNA-protein complexes by the CRM 1-dependent pathway, with special emphasis on the role of the Ran GTPase and associated proteins in this process.

Keywords

Nuclear Export Nuclear Import Nuclear Pore Complex Nuclear Export Signal Nuclear Retention 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Bryce M. Paschal
    • 1
  • Catherine Dargemont
    • 2
  1. 1.Center for Cell Signaling, Department of Biochemistry and Molecular GeneticsUniversity of VirginiaCharlottesvilleUSA
  2. 2.Institut Jacques Monod, UMR 7592ParisFrance

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