The Role of Ran in Nuclear Import

Abstract

The movement of macromolecules from the cytoplasm into the nucleus occurs through nuclear pore complexes (NPCs) in the nuclear envelope. NPCs are large organelles that bridge the double membrane of the nuclear envelope forming aqueous channels that connect the cytoplasm and nucleoplasm. The aqueous channels of NPCs are sufficiently large to permit the diffusion of small macromolecules from one compartment to the other, but most nuclear proteins contain a nuclear localization sequence (NLS) and are actively imported into the nucleus. NLSs are recognized by soluble nuclear carriers in the cytoplasm which, after binding their cargo, dock at the NPC. Import cargo:carrier complexes then move through the NPC in an energy-independent fashion by sequential binding to and release from multiple carrier binding sites located throughout the length of the NPC. In this way, the import cargo is moved from the cytoplasmic to the nucleoplasmic face of the NPC. There, the small GTPase Ran disrupts the cargo:carrier complex resulting in the release of cargo into the nuclear interior. This review will focus on the mechanism by which Ran catalyzes cargo release during nuclear import.