title: An alternative domain containing a leucine-rich sequence regulates nuclear cytoplasmic localization of protein 4.1R.
abstract: In red blood cells, protein 4.1 (4.1R) is an 80-kDa protein that stabilizes the spectrin-actin network and anchors it to the plasma membrane. The picture is more complex in nucleated cells, in which many 4.1R isoforms, varying in size and intracellular location, have been identified. To contribute to the characterization of signals involved in differential intracellular localization of 4.1R, we have analyzed the role the exon 5-encoded sequence plays in 4.1R distribution. We show that exon 5 encodes a leucine-rich sequence that shares key features with nuclear export signals (NESs). This sequence adopts the topology employed for NESs of other proteins and conserves two hydrophobic residues that are shown to be critical for NES function. A 4.1R isoform expressing the leucine-rich sequence binds to the export receptor CRM1 in a RanGTP-dependent fashion, whereas this does not occur in a mutant whose two conserved hydrophobic residues are substituted. These two residues are also essential for 4.1R intracellular distribution, because the 4.1R protein containing the leucine-rich sequence localizes in the cytoplasm, whereas the mutant protein predominantly accumulates in the nucleus. We hypothesize that the leucine-rich sequence in 4.1R controls distribution and concomitantly function of a specific set of 4.1R isoforms.
authors.affiliation: Departamento de Biologia Molecular, Centro de Biologia Molecular Severo Ochoa (Consejo Superior de Investigaciones Cientificas/Universidad Autónoma de Madrid), Universidad Autónoma de Madrid, Spain.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Luque
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Pérez-Ferreiro
authors.forename: Alicia
authors.initials: A
authors.lastname: Pérez-Gonzalez
authors.forename: Ludwig
authors.initials: L
authors.lastname: Englmeier
authors.forename: Maria D
authors.initials: MD
authors.lastname: Koffa
authors.forename: Isabel
authors.initials: I
authors.lastname: Correas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D049452:Green Fluorescent Proteins; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D007930:Leucine / Q000737:chemistry* / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009479:Neuropeptides; D014176:Protein Biosynthesis; D011487:Protein Conformation; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear; D014162:Transfection; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D049452:Green Fluorescent Proteins; D028884:Karyopherins; D007930:Leucine; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1