The GTPase @entity5856 is essential for nuclear import of proteins with a classical @entity2631 ( @entity2631 ). @entity5856 's @entity377 -bound state is determined by the chromatin-bound exchange factor @entity9605 generating RanGTP in the nucleus and the cytoplasmic GTPase activating protein @entity31222 depleting RanGTP from the cytoplasm. This predicts a steep RanGTP concentration gradient across the nuclear envelope. RanGTP binding to importin-beta has previously been shown to release importin-alpha from -beta during @entity2631 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 @entity31222 , the RanGTP binding protein @entity57629 or a @entity5856 mutant that cannot stably bind @entity3007 . 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 @entity2631 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-alpha and -beta, transportin, @entity645 Rev and tRNA appears to require nuclear RanGTP but may not require @entity3007 hydrolysis by @entity5856 , suggesting that the energy for their nuclear export is supplied by another source.

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

@entity3007 :: ('MESH:D006160', 'Chemical') :: ['GTP'] @entity9605 :: ('1104', 'Gene') :: ['RCC1'] @entity57629 :: ('5902', 'Gene') :: ['RanBP1'] @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide'] @entity645 :: ('57667', 'Species') :: ['HIV'] @entity2631 :: ('MESH:D012594', 'Disease') :: ['nuclear localization signal', 'NLS'] @entity5856 :: ('5901', 'Gene') :: ['Ran'] @entity31222 :: ('5905', 'Gene') :: ['RanGAP1']
@entity5856 :: (5901,Gene) :: ['Ran']
