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NTF2 mediates nuclear import of Ran

K Ribbeck1, G Lipowsky, H M Kent

  • 1Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.

The EMBO Journal
|November 21, 1998
PubMed
Summary
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Nuclear import of Ran, a key protein for nuclear transport, is facilitated by nuclear transport factor 2 (NTF2), not simple diffusion. This process requires NTF2 to bind RanGDP and is essential for maintaining nuclear protein transport.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Importin beta family receptors mediate nucleocytoplasmic transport via nuclear pore complexes (NPCs).
  • RanGTP regulates these interactions, necessitating continuous RanGTP replenishment in the nucleus as receptors exit with RanGTP.

Purpose of the Study:

  • To develop an in vitro system for studying nuclear Ran replenishment.
  • To elucidate the mechanism of nuclear import of Ran.

Main Methods:

  • Development of an in vitro system to study nuclear Ran import.
  • Analysis of Ran import using soluble transport factors and nuclear transport factor 2 (NTF2).
  • Investigation of the role of NTF2-RanGDP interaction using point mutations.

Related Experiment Videos

Main Results:

  • Nuclear import of Ran is not by diffusion but is facilitated by soluble factors.
  • Nuclear transport factor 2 (NTF2) specifically carries cytoplasmic RanGDP to NPCs.
  • A direct NTF2-RanGDP interaction is critical for Ran import; mutations disrupting this interaction impair import.
  • Nuclear accumulation of Ran requires GTP but not GTP hydrolysis.
  • Ran release into the nucleus involves nucleotide exchange to RanGTP, which then binds importin beta receptors.

Conclusions:

  • Nuclear transport factor 2 (NTF2) is the carrier for RanGDP import into the nucleus.
  • The NTF2-mediated import pathway is crucial for maintaining the RanGTP gradient necessary for nucleocytoplasmic transport.