Ran in nucleocytoplasmic transport

Abstract

The Ran GTPase is a crucial component of all nucleocytoplasmic transport pathways except those that mediate the nuclear export of mRNAs and ribosome subunits. The nucleotide state of Ran provides a means by which the cytoplasmic and nucleoplasmic compartments are recognized as a consequence of RCC1, the Ran guanine nucleotide exchange factor (RanGEF), being located in the nucleus, whereas the Ran GTPase activating protein, RanGAP, is located in the cytoplasm. This spatial arrangement of RanGEF and RanGAP results in nuclear Ran being primarily in the GTP-bound state whereas cytoplasmic Ran is in the GDP bound state. This distribution of Ran nucleotide state in turn mediates the binding and release of cargo macromolecules in the donor and target compartments, respectively. Generally the nucleocytoplasmic transport of macromolecules is mediated by transport factors of the karyopherin-β family that change their conformation depending on whether RanGTP is bound or not, and this conformational change in turn mediates the affinity of the transport factors for their cargoes.