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Title

The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus

Authors
Kutay, Ulrike
Mattaj, Iain W.
Görlich, Dirk
Published in EMBO Journal. 1997, vol. 16, no. 21, p. 6535-6547
Abstract The GTPase Ran is essential for nuclear import of proteins with a classical nuclear localization signal (NLS). Ran's nucleotide‐bound state is determined by the chromatin‐bound exchange factor RCC1 generating RanGTP in the nucleus and the cytoplasmic GTPase activating protein RanGAP1 depleting RanGTP from the cytoplasm. This predicts a steep RanGTP concentration gradient across the nuclear envelope. RanGTP binding to importin‐β has previously been shown to release importin‐α from ‐β during NLS import. We show that RanGTP also induces release of the M9 signal from the second identified import receptor, transportin. The role of RanGTP distribution is further studied using three methods to collapse the RanGTP gradient. Nuclear injection of either RanGAP1, the RanGTP binding protein RanBP1 or a Ran mutant that cannot stably bind GTP. These treatments block major export and import pathways across the nuclear envelope. Different export pathways exhibit distinct sensitivities to RanGTP depletion, but all are more readily inhibited than is import of either NLS or M9 proteins, indicating that the block of export is direct rather than a secondary consequence of import inhibition. Surprisingly, nuclear export of several substrates including importin‐α and ‐β, transportin, HIV Rev and tRNA appears to require nuclear RanGTP but may not require GTP hydrolysis by Ran, suggesting that the energy for their nuclear export is supplied by another source.
Keywords ImportinNuclear transportRanBP1RCC1Rna1Transportin
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Project FNS: 3100-046841
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IZAURRALDE, Elisa et al. The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus. In: EMBO Journal, 1997, vol. 16, n° 21, p. 6535-6547. doi: 10.1093/emboj/16.21.6535 https://archive-ouverte.unige.ch/unige:129035

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