title: Mammalian RanBP1 regulates centrosome cohesion during mitosis.
abstract: The Ran GTPase plays a central function in control of nucleo-cytoplasmic transport in interphase. Mitotic roles of Ran have also been firmly established in Xenopus oocyte extracts. In this system, Ran-GTP, or the RCC1 exchange factor for Ran, drive spindle assembly by regulating the availability of 'aster-promoting activities'. In previous studies to assess whether the Ran network also influences mitosis in mammalian cells, we found that overexpression of Ran-binding protein 1 (RanBP1), a major effector of Ran, induces multipolar spindles. We now show that these abnormal spindles are generated through loss of cohesion in mitotic centrosomes. Specifically, RanBP1 excess induces splitting of mother and daughter centrioles at spindle poles; the resulting split centrioles can individually organize functional microtubule arrays, giving rise to functional spindle poles. RanBP1-dependent centrosome splitting is specifically induced in mitosis and requires microtubule integrity and Eg5 activity. In addition, we have identified a fraction of RanBP1 at the centrosome. These data indicate that overexpressed RanBP1 interferes with crucial factor(s) that control structural and dynamic features of centrosomes during mitosis and contribute to uncover novel mitotic functions downstream of the Ran network.
authors.affiliation: CNR Institute of Molecular Biology and Pathology, Section of Genetics, c/o University 'La Sapienza', 00185 Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Di Fiore
authors.forename: Marilena
authors.initials: M
authors.lastname: Ciciarello
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Mangiacasale
authors.forename: Antonella
authors.initials: A
authors.lastname: Palena
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Tassin
authors.forename: Enrico
authors.initials: E
authors.lastname: Cundari
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lavia
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000378:metabolism*
chemical_list: C470243:KIF11 protein, human; D009687:Nuclear Proteins; C091775:ran-binding protein 1; D016547:Kinesins; D020931:ran GTP-Binding Protein