title: Requirement of guanosine triphosphate-bound ran for signal-mediated nuclear protein export.
abstract: A leucine-rich nuclear export signal (NES) allows rapid export of proteins from cell nuclei. Microinjection studies revealed a role for the guanosine triphosphatase (GTPase) Ran in NES-mediated export. Nuclear injection of a Ran mutant (Thr24 --> Asn) blocked protein export but not import, whereas depletion of the Ran nucleotide exchange factor RCC1 blocked protein import but not export. However, injection of Ran GTPase-activating protein (RanGAP) into RCC1-depleted cell nuclei inhibited export. Coinjection with Ran mutants insensitive to RanGAP prevented this inhibition. Therefore, NES-mediated protein export appears to require a Ran-GTP complex but does not require Ran-dependent GTP hydrolysis.
authors.affiliation: Department of Pathology, University of Vermont, Burlington, VT 05405, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Richards
authors.forename: K L
authors.initials: KL
authors.lastname: Carey
authors.forename: I G
authors.initials: IG
authors.lastname: Macara
mesh_terms: D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D006224:Cricetinae; D003593:Cytoplasm; D004268:DNA-Binding Proteins / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D020690:GTPase-Activating Proteins; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins; D020662:Guanine Nucleotide Exchange Factors; D006160:Guanosine Triphosphate / Q000378:metabolism*; D008164:Luminescent Proteins / Q000378:metabolism; D009154:Mutation; D009685:Nuclear Envelope / Q000378:metabolism; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013696:Temperature; D020931:ran GTP-Binding Protein
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D008164:Luminescent Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; C091775:ran-binding protein 1; D049452:Green Fluorescent Proteins; D006160:Guanosine Triphosphate; D005982:Glutathione Transferase; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020931:ran GTP-Binding Protein