Fig. 2.

Schematic representation of IMP/EXP dependent nucleocytoplasmic transport. Transport of NLS-containing cargo proteins from the cytoplasm to the nucleus is either mediated by IMPβs alone (1a), or the IMPα/β1 heterodimer (1b), where the IMPα adaptor links the cargo protein to IMPβ1. The IMP/cargo complexes then dock onto the cytoplasmic side of the NPC (2a and 2b), followed by passage to the nuclear side of the NPC, through sequential, transient interactions of the IMPβ with the FG-Nups that make up the NPC (3a and 3b). Once within the nucleus, RanGTP binding to IMPβ disassociates the complex (4a and 4b) to release the NLS-containing cargo into the nucleus to perform its function. In analogous fashion to nuclear import, transport of NES-containing cargo proteins (1c) from the nucleus to the cytoplasm is mediated by EXPs which recognise the NES, dependent on RanGTP binding to the EXP. The EXP/RanGTP/cargo complex docks at the nuclear side of the NPC (2c), before passing to the cytoplasmic side of NPC through sequential, transient interactions of the EXP with the FG-Nups (3c). Once within the cytoplasm, RanGAP1 (RanGTPase-activating protein 1) and RanBP1 facilitate hydrolysis of GTP to GDP by Ran (4c), thereby dissociating cargo from the EXP.