Mechanisms of receptor-mediated nuclear import and nuclear export.
Nuclear transport of proteins and RNA occurs through the nuclear pore complex and is mediated by a superfamily of transport receptors known collectively as karyopherins. Karyopherins bind to their cargoes by recognition of specific nuclear localization signals or nuclear export signals. Transport through the nuclear pore complex is facilitated by transient interactions between the karyopherins and the nuclear pore complex. The interactions of karyopherins with their cargoes are regulated by the Ras-related GTPase Ran. Ran is assisted in this process by proteins that regulate its GTPase cycle and subcellular localization. In this review, we describe several of the major transport pathways that are conserved in higher and lower eukaryotes, with particular emphasis on the role of Ran. We highlight the latest advances in the structure and function of transport receptors and discuss recent examples of steroid hormone receptor import and regulation by signal transduction pathways. Understanding the molecular basis of nuclear transport may provide insight into human diseases by revealing how nucleocytoplasmic trafficking regulates protein activity.
Pemberton
Lucy F
LF
Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908, USA.
Paschal
Bryce M
BM
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000502:physiology; D022022:Nuclear Pore / Q000502:physiology; D028861:Nuclear Pore Complex Proteins / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D034443:RNA Transport / Q000502:physiology*; D011987:Receptors, Steroid / Q000378:metabolism; D015398:Signal Transduction; D020931:ran GTP-Binding Protein / Q000502:physiology
D028884:Karyopherins; D009363:Neoplasm Proteins; D019913:Nuclear Localization Signals; D028861:Nuclear Pore Complex Proteins; D011987:Receptors, Steroid; D020931:ran GTP-Binding Protein