RanBP1 is crucial for the release of RanGTP from importin beta-related nuclear transport factors.
Nucleocytoplasmic transport appears mediated by shuttling transport receptors that bind RanGTP as a means to regulate interactions with their cargoes. The receptor-RanGTP complexes are kinetically very stable with nucleotide exchange and GTP hydrolysis being blocked, predicting that a specific disassembly mechanism exists. Here we show in three cases receptor RanGTP x RanBP1 complexes to be the key disassembly intermediates, where RanBP1 stimulates the off-rate at the receptor/RanGTP interface by more than two orders of magnitude. The transiently released RanGTP x RanBP1 complex is then induced by RanGAP to hydrolyse GTP, preventing the receptor to rebind RanGTP. The efficient release of importin beta from RanGTP requires importin alpha, in addition to RanBP1.
Bischoff
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Abteilung Molekulare Biologie der Mitose, Deutsches Krebsforschungszentrum, Heidelberg, Germany. R.Bischoff@dkfz-heidelberg.de
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D000818:Animals; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D028961:beta Karyopherins; D020931:ran GTP-Binding Protein
D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D028961:beta Karyopherins; C091775:ran-binding protein 1; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D020931:ran GTP-Binding Protein