Distinct nuclear import and export pathways mediated by members of the karyopherin beta family.
Transport of proteins into and out of the nucleus occurs through nuclear pore complexes (NPCs) and is mediated by the interaction of transport factors with nucleoporins at the NPC. Nuclear import of proteins containing classical nuclear localization signals (NLSs) is mediated by a heterodimeric protein complex, composed of karyopherin alpha and beta1, that docks via beta1 the NLS-protein to the NPC. The GTPase Ran; the RanGDP binding protein, p10; and the RanGTP binding protein, RanBP1 are involved in translocation of the docked NLS-protein into the nucleus. Recently, new distinct nuclear import and export pathways that are mediated by members of the karyopherin beta family have been discovered. Karyopherin beta2 mediates import of mRNA binding proteins, whereas karyopherin beta3 and beta4 mediate import of a set of ribosomal proteins. Two other beta karyopherin family members, CRM1 and CAS, mediate export of proteins containing leucine-rich nuclear export signals (NES) and reexport of karyopherin alpha, respectively. This growing family contains new members that constitute potential transport factors for cargoes yet to be identified in the future. The common features of the members of karyopherin beta family are the ability to bind RanGTP and the ability to interact directly with nucleoporins at the NPC. The challenge for the future will be to identify the distinct or, perhaps, overlapping cargo(es) for each member of the karyopherin beta superfamily and to characterize the molecular mechanisms of translocation of karyopherins together with their cargoes through the NPC.
Biology Department, Boston College, Chestnut Hill, Massachusetts 02167, USA. moroianu@bc.edu
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D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D028901:alpha Karyopherins; D028961:beta Karyopherins
D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D028901:alpha Karyopherins; D028961:beta Karyopherins