Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein export.
Crm1 is a member of the karyopherin family of nucleocytoplasmic transport receptors and mediates the export of proteins from the nucleus by forming a ternary complex with cargo and Ran:GTP. This complex translocates through the nuclear pores and dissociates in the cytosol. The yeast protein Yrb2p participates in this pathway and binds Crm1, but its mechanism of action has not been established. We show that the human orthologue of Yrb2p, Ran-binding protein 3 (RanBP3), acts as a cofactor for Crm1-mediated export in a permeabilized cell assay. RanBP3 binds directly to Crm1, and the complex possesses an enhanced affinity for both Ran:GTP and cargo. RanBP3 shuttles between the nucleus and the cytoplasm by a Crm1-dependent mechanism, and the Crm1--RanBP3-NES-Ran:GTP quarternary complex can associate with nucleoporins. We infer that this complex translocates through the nuclear pore to the cytoplasm where it is disassembled by RanBP1 and Ran GTPase--activating protein.
Lindsay
M E
ME
Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22098, USA. mel3f@virginia.edu
Holaska
J M
JM
Welch
K
K
Paschal
B M
BM
Macara
I G
IG
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D028884:Karyopherins; D046911:Macromolecular Substances; D022022:Nuclear Pore / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear; D012440:Saccharomyces; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D006160:Guanosine Triphosphate; D028884:Karyopherins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C112820:RANBP3 protein, human; C091775:ran-binding protein 1