A Role for RanBP1 in the Release of CRM1 from the Nuclear Pore Complex in a Terminal Step of Nuclear Export

doi:10.1083/jcb.145.4.645

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© The Rockefeller University Press, 0021-9525/1999//645 $5.00
The Journal of Cell Biology, Volume 145, Number 4, , 1999 645-657

Regular Articles

A Role for RanBP1 in the Release of CRM1 from the Nuclear Pore Complex in a Terminal Step of Nuclear Export

Ralph H. Kehlenbach, Achim Dickmanns, Angelika Kehlenbach, Tinglu Guan, and Larry Gerace

Departments of Cell Biology and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037

We recently developed an assay in which nuclear export of theshuttling transcription factor NFAT (nuclear factor of activatedT cells) can be reconstituted in permeabilized cells with theGTPase Ran and the nuclear export receptor CRM1. We have nowused this assay to identify another export factor. After preincubationof permeabilized cells with a Ran mutant that cannot hydrolyzeGTP (RanQ69L), cytosol supports NFAT export, but CRM1 and Ranalone do not. The RanQ69L preincubation leads to accumulationof CRM1 at the cytoplasmic periphery of the nuclear pore complex(NPC) in association with the p62 complex and Can/Nup214. RanGTP-dependentassociation of CRM1 with these nucleoporins was reconstitutedin vitro. By biochemical fractionation and reconstitution, we showed that RanBP1 restores nuclear export after the RanQ69Lpreincubation. It also stimulates nuclear export in cells thathave not been preincubated with RanQ69L. RanBP1 as well asRan-binding domains of the cytoplasmic nucleoporin RanBP2 promotethe release of CRM1 from the NPC. Taken together, our resultsindicate that RanGTP is important for the targeting of exportcomplexes to the cytoplasmic side of the NPC and that RanBP1and probably RanBP2 are involved in the dissociation of nuclearexport complexes from the NPC in a terminal step of transport.

Key Words: nuclear transport • CRM1 • Ran • RanBP1

Abbreviations used in this paper: cc, cytochrome c; GFP, green fluorescent protein; GST, glutathione-S-transferase; NE, nuclear envelope; NES, nuclear export sequence; NFAT, nuclear factor of activated T cells; NLS, nuclear localization sequence; NPC, nuclear pore complex; RBD, Ran-binding domain.

Dr. Dickmanns' present address is Max Planck Institut fürBiochemie, Am Klopferspitz 18a, D-82152 Martinsried, Germany.

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