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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
Summary
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.
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.