Molecular mechanisms of nuclear protein transport.
Transport of proteins into and out of the nucleus occurs through nuclear pore complexes (NPC). A heterodimeric protein complex, composed of karyopherin alpha and beta (or importin alpha and beta) functions to target proteins containing a nuclear localization sequence (NLS) to the NPCs. Two additional proteins, the GTPase Ran and p10, are required to translocate the docked NLS protein into the nucleus. The alpha subunit of karyopherin functions as the NLS receptor, whereas the beta subunit mediates docking to nucleoporins that contain peptide repeats. During import the karyopherin heterodimer dissociates: karyopherin alpha and import substrates enter and accumulate in the nucleoplasm, whereas karyopherin beta accumulates at the nuclear pore complex. Ran-GTP induces dissociation of karyopherin alpha from beta by forming a complex with karyopherin beta and promotes the release of both karyopherin subunits from a docking site. Protein transport across the NPC may occur via guided diffusion involving the karyopherin-mediated docking and undocking of import substrate to multiple binding sites that extend from the cytoplasmic to the nucleoplasmic ends of the NPC.
Moroianu
J
J
Laboratory of Cell Biology, Rockefeller University, New York, NY 10021, USA.
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins; D009685:Nuclear Envelope / Q000737:chemistry; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D029867:Xenopus Proteins; D028901:alpha Karyopherins; D028961:beta Karyopherins; D020931:ran GTP-Binding Protein
D002352:Carrier Proteins; D028884:Karyopherins; C499531:NTF2 protein, S cerevisiae; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; C089822:Ran-interacting protein p10, Xenopus; D029701:Saccharomyces cerevisiae Proteins; D029867:Xenopus Proteins; D028901:alpha Karyopherins; D028961:beta Karyopherins; D020931:ran GTP-Binding Protein