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

• Published in: Cell 1997-09, Vol.90 (6), p.1061-1071
• Main Authors: Kutay, Ulrike, Bischoff, F.Ralf, Kostka, Susanne, Kraft, Regine, Görlich, Dirk
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - physiology; Biological Transport - physiology; Carrier Proteins - metabolism; Cellular Apoptosis Susceptibility Protein; Cytoplasm - metabolism; GTP-Binding Proteins - metabolism; HeLa Cells; Humans; Karyopherins; Leucine Zippers - physiology; Nuclear Envelope - metabolism; Nuclear Proteins - metabolism; Oocytes - physiology; Protein Binding - physiology; Proteins - metabolism; ran GTP-Binding Protein; Recombinant Proteins - metabolism; Solubility; Xenopus
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80372-4

NLS 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.