The direction of transport through the nuclear pore can be inverted

Transport of macromolecules across the nuclear envelope is an active proces s that depends on soluble factors including the GTPase Ran. Ran-GTP is pred ominantly located in the nucleus and has been shown to regulate cargo bindi ng and release of import and export receptors in their respective target co mpartments. Recently, it was shown that transport of receptor-cargo complex es across the nuclear pore complex (NPC) does not depend on GTP-hydrolysis by Ran; holt;ever, the mechanism of translocation is still poorly understoo d. Were, we show that the direction of transport through the NPC can be inv erted in the presence of high concentrations of cytoplasmic Ran-GTP. Under these conditions, two different classes of export cargoes are transported i nto the nucleus in the absence of GTP hydrolysis. The inverted transport is very rapid and can be blocked by known inhibitors of nuclear protein expor t. These results suggest that the NPC functions as a facilitated transport channel, allowing the selective translocation of receptor-cargo complexes, We conclude that the directionality of nucleocytoplasmic transport is deter mined mainly by the compartmentalized distribution of Ran-GTP.