SAK/PLK4 Is Required for Centriole Duplication and Flagella Development

• DOI: 10.1016/j.cub.2005.11.042
• Publication Date: 2005-12-02T12:29:15Z
• Authors: M. Bettencourt-Dias; A. Rodrigues-Martins; L. Carpenter; M. Riparbelli; L. Lehmann; M.K. Gatt; N. Carmo; F. Balloux; G. Callaini; D.M. Glover
• Keywords: 570; 0303 health sciences; Agricultural and Biological Sciences(all); Biochemistry, Genetics and Molecular Biology(all); Mitosis; Spindle Apparatus; Protein Serine-Threonine Kinases; Models, Biological; Animals; Cells, Cultured; Centrioles/genetics; Centrioles/physiology; Drosophila; Flagella/genetics; Flagella/physiology; Humans; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Mitosis/physiology; Mitotic Spindle Apparatus/physiology; Models, Biological; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; RNA Interference; 03 medical and health sciences; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Flagella; Animals; Humans; Drosophila; RNA Interference; Cells, Cultured; Centrioles

SAK/PLK4 is a distinct member of the polo-like kinase family. SAK-/- mice die during embryogenesis, whereas SAK+/- mice develop liver and lung tumors and SAK+/- MEFs show mitotic abnormalities. However, the mechanism underlying these phenotypes is still not known.Here, we show that downregulation of SAK in Drosophila cells, by mutation or RNAi, leads to loss of centrioles, the core structures of centrosomes. Such cells are able to undergo repeated rounds of cell division, but display broad disorganized mitotic spindle poles. We also show that SAK mutants lose their centrioles during the mitotic divisions preceding male meiosis but still produce cysts of 16 primary spermatocytes as in the wild-type. Mathematical modeling of the stereotyped cell divisions of spermatogenesis can account for such loss by defective centriole duplication. The majority of spermatids in SAK mutants lack centrioles and so are unable to make sperm axonemes. Finally, we show that depletion of SAK in human cells also prevents centriole duplication and gives rise to mitotic abnormalities.SAK/PLK4 is necessary for centriole duplication both in Drosophila and human cells. Drosophila cells tolerate the lack of centrioles and undertake mitosis but cannot form basal bodies and hence flagella. Human cells depleted of SAK show error-prone mitosis, likely to underlie its tumor-suppressor role.