Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor

Cell. 1997 Sep 19;90(6):1061-71. doi: 10.1016/s0092-8674(00)80372-4.

Abstract

NLS proteins are transported into the nucleus by the importin alpha/beta heterodimer. Importin alpha binds the NLS, while importin beta mediates translocation through the nuclear pore complex. After translocation, RanGTP, whose predicted concentration is high in the nucleus and low in the cytoplasm, binds importin beta and displaces importin alpha. Importin alpha must then be returned to the cytoplasm, leaving the NLS protein behind. Here, we report that the previously identified CAS protein mediates importin alpha re-export. CAS binds strongly to importin alpha only in the presence of RanGTP, forming an importin alpha/CAS/RanGTP complex. Importin alpha is released from this complex in the cytoplasm by the combined action of RanBP1 and RanGAP1. CAS binds preferentially to NLS-free importin alpha, explaining why import substrates stay in the nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Biological Transport / physiology
  • Carrier Proteins / metabolism
  • Cellular Apoptosis Susceptibility Protein
  • Cytoplasm / metabolism
  • GTP-Binding Proteins / metabolism
  • HeLa Cells
  • Humans
  • Karyopherins
  • Leucine Zippers / physiology
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / metabolism*
  • Oocytes / physiology
  • Protein Binding / physiology
  • Proteins / metabolism
  • Recombinant Proteins / metabolism
  • Solubility
  • Xenopus
  • ran GTP-Binding Protein

Substances

  • Carrier Proteins
  • Cellular Apoptosis Susceptibility Protein
  • Karyopherins
  • Nuclear Proteins
  • Proteins
  • Recombinant Proteins
  • ran-binding protein 1
  • GTP-Binding Proteins
  • ran GTP-Binding Protein