Export of Importin α from the Nucleus Is Mediated by a Specific Nuclear Transport Factor

AbstractNLS proteins are transported into the nucleus by the importin α/β heterodimer. Importin α binds the NLS, while importin β mediates translocation through the nuclear pore complex. After translocation, RanGTP, whose predicted concentration is high in the nucleus and low in the cytoplasm, binds importin β and displaces importin α. Importin α must then be returned to the cytoplasm, leaving the NLS protein behind. Here, we report that the previously identified CAS protein mediates importin α re-export. CAS binds strongly to importin α only in the presence of RanGTP, forming an importin α/CAS/RanGTP complex. Importin α is released from this complex in the cytoplasm by the combined action of RanBP1 and RanGAP1. CAS binds preferentially to NLS-free importin α, explaining why import substrates stay in the nucleus

Human RanBP3, a group of nuclear RanGTP binding proteins1The nucleotide and amino acid sequence data reported in this paper have been deposited in the EMBL, GenBank and DDBJ Nucleotide Sequence Databases under the accession numbers Y08697, Y08698 and Y08699.1

AbstractA group of novel human Ran-binding proteins, RanBP3, was identified using the yeast two-hybrid system via Ran-mediated interaction with the nucleotide exchange factor RCC1. Several open reading frames, representing putative alternatively spliced products, were established by cDNA cloning. Two of them, RanBP3-a and RanBP3-b, encode nuclear hydrophilic proteins of 499 and 562 amino acid residues. The sequences contain FXFG motifs, characteristic of a subgroup of nucleoporins, and a C-terminal domain showing similarity to the Ran-binding protein RanBP1. These proteins are localized in the nucleus, preferentially bind RanGTP and may be nuclear effectors of the Ran pathway

Exportin 4: a mediator of a novel nuclear export pathway in higher eukaryotes

Transport receptors of the importin β superfamily account for many of the nuclear import and export events in eukaryotic cells. They mediate translocation through nuclear pore complexes, shuttle between nucleus and cytoplasm and co-operate with the RanGTPase system to regulate their interactions with cargo molecules in a compartment-specific manner. We used affinity chromatography on immobilized RanGTP to isolate further candidate nuclear transport receptors and thereby identified exportin 4 as the most distant member of the importin β family so far. Exportin 4 appears to be conserved amongst higher eukaryotes, but lacks obvious orthologues in yeast. It mediates nuclear export of eIF-5A (eukaryotic translation initiation factor 5A) and possibly that of other cargoes. The export signal in eIF-5A appears to be complex and to involve the hypusine modification that is unique to eIF-5A. We discuss possible cellular roles for nuclear export of eIF-5A