title: Nek9 phosphorylation of NEDD1/GCP-WD contributes to Plk1 control of γ-tubulin recruitment to the mitotic centrosome.
abstract: The accumulation of γ-tubulin at the centrosomes during maturation is a key mechanism that ensures the formation of two dense microtubule (MT) asters in cells entering mitosis, defining spindle pole positioning and ensuring the faithful outcome of cell division. Centrosomal γ-tubulin recruitment depends on the adaptor protein NEDD1/GCP-WD and is controlled by the kinase Plk1. Surprisingly, and although Plk1 binds and phosphorylates NEDD1 at multiple sites, the mechanism by which this kinase promotes the centrosomal recruitment of γ-tubulin has remained elusive. Using Xenopus egg extracts and mammalian cells, we now show that it involves Nek9, a NIMA-family kinase required for normal mitotic progression and spindle organization. Nek9 phosphorylates NEDD1 on Ser377 driving its recruitment and thereby that of γ-tubulin to the centrosome in mitotic cells. This role of Nek9 requires its activation by Plk1-dependent phosphorylation but is independent from the downstream related kinases Nek6 and Nek7. Our data contribute to understand the mechanism by which Plk1 promotes the recruitment of γ-tubulin to the centrosome in dividing cells and position Nek9 as a key regulator of centrosome maturation.
authors: Cell Signaling Research Group, Molecular Medicine Program, Institute for Research in Biomedicine (IRB Barcelona), Baldiri i Reixac, 10-12, 08028 Barcelona, Spain.
authors: Sara
authors: S
authors: Sdelci
authors: Martin
authors: M
authors: Schütz
authors: Roser
authors: R
authors: Pinyol
authors: M Teresa
authors: MT
authors: Bertran
authors: Laura
authors: L
authors: Regué
authors: Carme
authors: C
authors: Caelles
authors: Isabelle
authors: I
authors: Vernos
authors: Joan
authors: J
authors: Roig
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018385:Centrosome / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000502:physiology; D008938:Mitosis; D000072379:NIMA-Related Kinases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011817:Rabbits; D014404:Tubulin / Q000378:metabolism*; D014981:Xenopus; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D014404:Tubulin; D000097869:Polo-Like Kinase 1; C509189:NEDD1 protein, human; C462119:NEK9 protein, human