Figure 3. The GTPase Ran drives the nuclear transport cycle. Importin-β transport receptors recognize their NLS-containing cargo proteins in the cytoplasm and promote nuclear translocation of the importin-cargo complex across the NPC. Binding of RanGTP to the importin-β transport receptor in the nucleoplasm leads to the dissociation of the cargo protein. The RanGTP-bound transport receptor returns to the cytoplasm where Ran-GAP stimulation of GTP hydrolysis releases RanGDP. To replenish the pool of nuclear RanGTP, NTF2 re-imports RanGDP into the nucleus where the chromatin-associated Ran-GEF promotes GTP loading of Ran.