title: Drosophila Nek2 protein kinase knockdown leads to centrosome maturation defects while overexpression causes centrosome fragmentation and cytokinesis failure.
abstract: The Nima-related kinase 2 (Nek2) has been implicated in the regulation of centrosome integrity and separation in several species and is a candidate for cell transformation. We now show that reduction of levels of the Drosophila Nek2 by RNAi in cultured cells leads to both dispersal of centrosomal antigens and formation of ectopic bodies of centrosomal antigens. Overexpression of the active DmNek2 kinase resulted in an increase in the number of mitotic cells with fragmented centrosomes. The DmNek2 protein kinase is associated with punctuate bodies within the centrosome consistent with its presence on centrioles. In addition, it is present at lower levels on the midbody during cytokinesis. Midbody association was enhanced following overexpression, whereupon the DmNek2 protein kinase also localised to the cell cortex becoming concentrated in the region of the cleavage furrow in late telophase. Many of such cells showed abnormalities in the organisation of anillin and actin in the cleavage furrow that was associated with formation of ectopic membrane protrusions between each daughter cell. We discuss potential roles for DmNek2 in maintaining centrosome integrity in mitosis, during cytokinesis, and consequently for the fidelity of chromosome segregation.
authors.affiliation: Groupe Cycle Cellulaire, UMR6061 Génétique et Développement, CNRS-Université de Rennes 1, IFR97 Génomique Fonctionnelle et Santé, 35043 Rennes Cedex, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Prigent
authors.forename: David M
authors.initials: DM
authors.lastname: Glover
authors.forename: Régis
authors.initials: R
authors.lastname: Giet
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism*; D003285:Contractile Proteins / Q000378:metabolism*; D048749:Cytokinesis / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000199:Actins; D003285:Contractile Proteins; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; C095886:anillin; C000620809:Nek2 protein, Drosophila; D017346:Protein Serine-Threonine Kinases