title: Identification of a polo-like kinase 4-dependent pathway for de novo centriole formation.
abstract: Supernumerary centrosomes are a key cause of genomic instability in cancer cells. New centrioles can be generated by duplication with a mother centriole as a platform or, in the absence of preexisting centrioles, by formation de novo. Polo-like kinase 4 (Plk4) regulates both modes of centriole biogenesis, and Plk4 deregulation has been linked to tumor development. We show that Plx4, the Xenopus homolog of mammalian Plk4 and Drosophila Sak, induces de novo centriole formation in vivo in activated oocytes and in egg extracts, but not in immature or in vitro matured oocytes. Both kinase activity and the polo-box domain of Plx4 are required for de novo centriole biogenesis. Polarization microscopy in "cycling" egg extracts demonstrates that de novo centriole formation is independent of Cdk2 activity, a major difference compared to template-driven centrosome duplication that is linked to the nuclear cycle and requires cyclinA/E/Cdk2. Moreover, we show that the Mos-MAPK pathway blocks Plx4-dependent de novo centriole formation before fertilization, thereby ensuring paternal inheritance of the centrosome. The results define a new system for studying the biochemical and molecular basis of de novo centriole formation and centriole biogenesis in general.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Eckerdt
authors.forename: Tomomi M
authors.initials: TM
authors.lastname: Yamamoto
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Lewellyn
authors.forename: James L
authors.initials: JL
authors.lastname: Maller
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002502:Centrioles / Q000378:metabolism*; D008859:Microscopy, Polarization; D009865:Oocytes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D029867:Xenopus Proteins; D017346:Protein Serine-Threonine Kinases; C559282:polo-like kinase 4, Xenopus