title: The importin beta/importin 7 heterodimer is a functional nuclear import receptor for histone H1.
abstract: Import of proteins into the nucleus proceeds through nuclear pore complexes and is largely mediated by nuclear transport receptors of the importin beta family that use direct RanGTP-binding to regulate the interaction with their cargoes. We investigated nuclear import of the linker histone H1 and found that two receptors, importin beta (Impbeta) and importin 7 (Imp7, RanBP7), play a critical role in this process. Individually, the two import receptors bind H1 weakly, but binding is strong for the Impbeta/Imp7 heterodimer. Consistent with this, import of H1 into nuclei of permeabilized mammalian cells requires exogenous Impbeta together with Imp7. Import by the Imp7/Impbeta heterodimer is strictly Ran dependent, the Ran-requiring step most likely being the disassembly of the cargo-receptor complex following translocation into the nucleus. Disassembly is brought about by direct binding of RanGTP to Impbeta and Imp7, whereby the two Ran-binding sites act synergistically. However, whereas an Impbeta/RanGTP interaction appears essential for H1 import, Ran-binding to Imp7 is dispensable. Thus, Imp7 can function in two modes. Its Ran-binding site is essential when operating as an autonomous import receptor, i.e. independently of Impbeta. Within the Impbeta/Imp7 heterodimer, however, Imp7 plays a more passive role than Impbeta and resembles an import adapter.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jäkel
authors.forename: W
authors.initials: W
authors.lastname: Albig
authors.forename: U
authors.initials: U
authors.lastname: Kutay
authors.forename: F R
authors.initials: FR
authors.lastname: Bischoff
authors.forename: K
authors.initials: K
authors.lastname: Schwamborn
authors.forename: D
authors.initials: D
authors.lastname: Doenecke
authors.forename: D
authors.initials: D
authors.lastname: Görlich
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D019281:Dimerization; D006160:Guanosine Triphosphate / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D028884:Karyopherins; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014981:Xenopus; D020931:ran GTP-Binding Protein
chemical_list: D006657:Histones; D028884:Karyopherins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D006160:Guanosine Triphosphate; D020931:ran GTP-Binding Protein