title: The adapter importin-alpha provides flexible control of nuclear import at the expense of efficiency.
abstract: Although there exists a large family of nuclear transport receptors (Karyopherins), the majority of known import cargoes use an adapter protein, Importin-alpha (Impalpha), which links the cargo to a karyopherin, Importin-beta (Impbeta). The reason for the existence of transport adapters is unknown. One hypothesis is that, as Impalpha re-export is coupled to GTP hydrolysis, it can drive a higher concentration of nuclear cargo than could be achieved by direct cargo binding to Importin-beta. However, computer simulations predicted the opposite outcome, and showed that direct transport is faster than adapter-mediated transport. These predictions were validated experimentally. The data, together with previous analyses of nuclear protein import, suggest that the use of adapters such as importin-alpha provides the cell with increased dynamic range for control of nuclear import rates, but at the expense of efficiency.
authors.affiliation: Department of Biochemistry, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Riddick
authors.forename: Ian G
authors.initials: IG
authors.lastname: Macara
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D028901:alpha Karyopherins / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D028901:alpha Karyopherins; D000097606:Exportin 1 Protein