EXPORT OF IMPORTIN-ALPHA FROM THE NUCLEUS IS MEDIATED BY A SPECIFIC NUCLEAR TRANSPORT FACTOR

NLS proteins are transported into the nucleus by the importin alpha/be ta heterodimer. Importin alpha binds the NLS, while importin beta medi ates translocation through the nuclear pore complex. After translocati on, RanGTP, whose predicted concentration is high in the nucleus and l ow in the cytoplasm, binds importin beta and displaces importin alpha. Importin alpha must then be returned to the cytoplasm, leaving the NL S protein behind. Here, we report that the previously identified CAS p rotein mediates importin alpha re-export. CAS binds strongly to import in alpha only in the presence of RanGTP, forming an importin alpha/CAS /RanGTP complex. Importin alpha is released from this complex in the c ytoplasm by the combined action of RanBP1 and RanGAP1. CAS binds prefe rentially to NLS-free importin alpha, explaining why import substrates stay in the nucleus.