FIGURE 13-37 Ran-dependent and Ran-independent nuclear export. (a) Ran-dependent mechanism for nuclear export of cargo proteins containing a leucine-rich nuclear-export signal (NES). In the nucleoplasm (bottom), the protein exportin 1 binds cooperatively to the NES of the cargo protein to be transported and to Ran·GTP. After the resulting cargo complex diffuses through an NPC via transient interactions with FG-repeats in FG-nucleoporins, the GAP associated with the NPC cytoplasmic filaments stimulates GTP hydrolysis, converting Ran·GTP to Ran·GDP. The accompanying conformational change in Ran leads to dissociation of the complex. The NES-containing cargo protein is released into the cytosol, whereas exportin 1 and Ran·GDP are transported back into the nucleus through an NPC. Ran-GEF in the nucleoplasm then stimulates conversion of Ran·GDP to Ran·GTP. (b) Ran-independent nuclear export of mRNAs. The heterodimeric NXF1/NXT1 complex binds to mRNA-protein complexes (mRNPs) in the nucleus. NXF1/NXT1 acts as a nuclear transport receptor and directs the associated mRNP to the central channel of the NPC by transiently interacting with FG-nucleoporins. An RNA helicase (Dbp5) located on the cytoplasmic side of the NPC removes NXF1 and NXT1 from the mRNA in a reaction that is powered by ATP hydrolysis. Free NXF1 and NXT1 proteins are recycled back into the nucleus by the Ran-dependent import process depicted in Figure 13-36.