title: Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion in mitosis.
abstract: Nek5 is a poorly characterized member of the NIMA-related kinase family, other members of which play roles in cell cycle progression and primary cilia function. Here, we show that Nek5, similar to Nek2, localizes to the proximal ends of centrioles. Depletion of Nek5 or overexpression of kinase-inactive Nek5 caused unscheduled separation of centrosomes in interphase, a phenotype also observed upon overexpression of active Nek2. However, separated centrosomes that resulted from Nek5 depletion remained relatively close together, exhibited excess recruitment of the centrosome linker protein rootletin, and had reduced levels of Nek2. In addition, Nek5 depletion led to loss of PCM components, including γ-tubulin, pericentrin, and Cdk5Rap2, with centrosomes exhibiting reduced microtubule nucleation. Upon mitotic entry, Nek5-depleted cells inappropriately retained centrosome linker components and exhibited delayed centrosome separation and defective chromosome segregation. Hence, Nek5 is required for the loss of centrosome linker proteins and enhanced microtubule nucleation that lead to timely centrosome separation and bipolar spindle formation in mitosis.
authors.affiliation: Department of Biochemistry, University of Leicester, Leicester LE1 9HN, England, UK Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada prosser@lunenfeld.ca amf5@le.ac.uk.
authors.forename: Suzanna L
authors.initials: SL
authors.lastname: Prosser
authors.affiliation: Department of Biochemistry, University of Leicester, Leicester LE1 9HN, England, UK.
authors.forename: Navdeep K
authors.initials: NK
authors.lastname: Sahota
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Pelletier
authors.affiliation: Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
authors.forename: Ciaran G
authors.initials: CG
authors.lastname: Morrison
authors.affiliation: Department of Biochemistry, University of Leicester, Leicester LE1 9HN, England, UK prosser@lunenfeld.ca amf5@le.ac.uk.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Fry
mesh_terms: D000941:Antigens / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D018797:Cell Cycle Proteins; D018385:Centrosome / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007399:Interphase / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D000941:Antigens; C405929:CDK5RAP2 protein, human; C499237:CROCC protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D014404:Tubulin; C086178:pericentrin; D011494:Protein Kinases