title: NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytoplasmic shuttling protein associated with active synaptoneurosomes.
abstract: Fragile X syndrome, the most common cause of inherited mental retardation, is caused by the absence of FMRP (Fragile X Mental Retardation Protein). FMRP is an RNA binding protein reported to be involved in translational control, notably at postsynaptic sites of protein synthesis as a part of a multiprotein/mRNA complex. One of the FMRP interactors, NUFIP1, is an RNA binding protein with an expression profile matching that of FMRP. We now show that in the nucleus NUFIP1 is localized in the nuclear matrix in RNA-containing structures lying in the proximity of, but not overlapping with, sites of nascent RNA. NUFIP1 is also present in the cytoplasm, where it is associated with ribosomes, similarly to FMRP. In neurons NUFIP1 can be detected in functional synaptoneurosomes, colocalizing with ribosomes. Consistent with its subcellular localization in both nucleus and cytoplasm, we show that NUFIP1 contains a functional CRM1-dependent nuclear export signal and is able to shuttle between these two cellular compartments. These findings suggest the involvement of NUFIP1 in the export and localization of mRNA and, in association with FMRP, in the regulation of local protein synthesis near synapses.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 10142, 67404 Illkirch, C.U. de Strasbourg, France. bardoni@igbmc.u-strasbg.fr
authors.forename: Barbara
authors.initials: B
authors.lastname: Bardoni
authors.forename: Rob
authors.initials: R
authors.lastname: Willemsen
authors.forename: Ivan Jeanne
authors.initials: IJ
authors.lastname: Weiler
authors.forename: Annette
authors.initials: A
authors.lastname: Schenck
authors.forename: Lies-Anne
authors.initials: LA
authors.lastname: Severijnen
authors.forename: Colette
authors.initials: C
authors.lastname: Hindelang
authors.forename: Enzo
authors.initials: E
authors.lastname: Lalli
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mandel
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D002451:Cell Compartmentation / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015530:Nuclear Matrix / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D014176:Protein Biosynthesis / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction / Q000235:genetics; D013574:Synaptosomes; D013737:Testis / Q000378:metabolism / Q000648:ultrastructure; D000097606:Exportin 1 Protein
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D028884:Karyopherins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012313:RNA; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse; C497685:Fmr1 protein, rat; C403092:NUFIP1 protein, human