title: The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions.
abstract: We previously demonstrated that a fraction of the human Nup107-160 nuclear pore subcomplex is recruited to kinetochores at the onset of mitosis. However, the molecular determinants for its kinetochore targeting and the functional significance of this localization were not investigated. Here, we show that the Nup107-160 complex interacts with CENP-F, but that CENP-F only moderately contributes to its targeting to kinetochores. In addition, we show that the recruitment of the Nup107-160 complex to kinetochores mainly depends on the Ndc80 complex. We further demonstrate that efficient depletion of the Nup107-160 complex from kinetochores, achieved either by combining siRNAs targeting several of its subunits excluding Seh1, or by depleting Seh1 alone, induces a mitotic delay. Further analysis of Seh1-depleted cells revealed impaired chromosome congression, reduced kinetochore tension and kinetochore-microtubule attachment defects. Finally, we show that the presence of the Nup107-160 complex at kinetochores is required for the recruitment of Crm1 and RanGAP1-RanBP2 to these structures. Together, our data thus provide the first molecular clues underlying the function of the human Nup107-160 complex at kinetochores.
authors.affiliation: Centre de Recherche, UMR 144 CNRS, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Michela
authors.initials: M
authors.lastname: Zuccolo
authors.forename: Annabelle
authors.initials: A
authors.lastname: Alves
authors.forename: Vincent
authors.initials: V
authors.lastname: Galy
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bolhy
authors.forename: Etienne
authors.initials: E
authors.lastname: Formstecher
authors.forename: Victor
authors.initials: V
authors.lastname: Racine
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Sibarita
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Fukagawa
authors.forename: Ramin
authors.initials: R
authors.lastname: Shiekhattar
authors.forename: Tim
authors.initials: T
authors.lastname: Yen
authors.forename: Valérie
authors.initials: V
authors.lastname: Doye
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002877:Chromosomes, Human / Q000378:metabolism; D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008677:Metaphase; D008840:Microfilament Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D049468:Prometaphase; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D008840:Microfilament Proteins; D015778:Minor Histocompatibility Antigens; D018832:Molecular Chaperones; C120529:NDC80 protein, human; C512772:NUP107 protein, human; C440250:NUP133 protein, human; C440251:NUP160 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C092317:RANGAP1 protein, human; C094772:centromere protein F; C094493:ran-binding protein 2