title: Transportin: nuclear transport receptor of a novel nuclear protein import pathway.
abstract: Many nuclear proteins are imported into the cell nucleus by the "classical" nuclear localization signal (NLS)-mediated import pathway. In this pathway, a sequence rich in basic residues in the protein interacts with a heterodimeric complex termed importin and this, along with the GTPase Ran, mediates nuclear import of the NLS-bearing protein. The heterogeneous nuclear ribonucleoprotein (hnRNP) A1 protein contains a novel nuclear localization sequence, termed M9, that does not contain any clusters of basic residues. Very recently, we showed that M9 directs import into the nucleus by a novel protein import pathway distinct from the classical NLS pathway. A 90-kilodalton protein termed transportin was identified as a protein that specifically interacts with wild-type M9 but not transport-defective M9 mutants. Transportin and an ATP-regenerating system were found to be necessary and sufficient for import of M9-containing proteins in an in vitro import assay. In this report, we provide additional evidence that transportin can interact directly with M9-containing proteins and also show that it can mediate import of full-length hnRNP A1. In addition, Ran, or a Ran-binding protein, is identified as a second protein component of this novel nuclear import pathway. Transportin relatives from Saccharomyces cerevisiae which likely serve as additional nuclear transport receptors are described.
authors.affiliation: Howard Hughes Medical Institute, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, 19104-6148, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nakielny
authors.forename: M C
authors.initials: MC
authors.lastname: Siomi
authors.forename: H
authors.initials: H
authors.lastname: Siomi
authors.forename: W M
authors.initials: WM
authors.lastname: Michael
authors.forename: V
authors.initials: V
authors.lastname: Pollard
authors.forename: G
authors.initials: G
authors.lastname: Dreyfuss
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006367:HeLa Cells; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D066298:In Vitro Techniques; D028884:Karyopherins; D008954:Models, Biological; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D020931:ran GTP-Binding Protein
chemical_list: D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D028884:Karyopherins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012261:Ribonucleoproteins; D020558:GTP Phosphohydrolases; D020931:ran GTP-Binding Protein