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SAK/PLK4 Is Required for Centriole Duplication and Flagella Development

Bettencourt-Dias, M. and Rodrigues-Martins, A. and Carpenter, L. and Riparbelli, M. and Lehmann, L. and Gatt, M. K. and Carmo, N. and Balloux, F. and Callaini, G. and Glover, D. M. (2005) SAK/PLK4 Is Required for Centriole Duplication and Flagella Development. Current Biology, 15 (24). pp. 2199-2207. ISSN 0960-9822. doi:10.1016/j.cub.2005.11.042.

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Background. 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. Results. 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. Conclusions: 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.

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Glover, D. M.0000-0003-0956-0103
Additional Information:© 2005 Elsevier Under an Elsevier user license. Received 30 September 2005, Revised 27 October 2005, Accepted 11 November 2005, Available online 1 December 2005. We are grateful to grants from Cancer Research UK to support this work in the CRUK Cell Cycle Genetics Research Group. We thank Jordan Raff, Michel Bornens, Jeff Salisbury, and Carsten Janke for reagents. We also thank Adelaide Carpenter, Ryoko Kuryama, Jose Pereira-Leal, Renata Basto, Natalie Delgehyr, Simon Tavaré, and Marek Kimmel for discussions and comments on the manuscript. Note Added in Proof: While this manuscript was under review, another study reported a role for SAK/PLK4 in centrosome duplication: Habedanck, R., Stierhof, Y.-D., Wilkinson, C.J., and Nigg, E.A. (2005). The Polo kinase Plk4 functions in centriole duplication. Nat. Cell Biol. 7, 1140–1146. Published online October 23, 2005. 10.1038/ncb1320. This version differs slightly from the one originally published online in that italics and uppercase letters have been added in a few places to suit the correct genetic nomenclature.
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Issue or Number:24
Record Number:CaltechAUTHORS:20200806-163116104
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Official Citation:M. Bettencourt-Dias, A. Rodrigues-Martins, L. Carpenter, M. Riparbelli, L. Lehmann, M.K. Gatt, N. Carmo, F. Balloux, G. Callaini, D.M. Glover, SAK/PLK4 Is Required for Centriole Duplication and Flagella Development, Current Biology, Volume 15, Issue 24, 2005, Pages 2199-2207, ISSN 0960-9822,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104793
Deposited By: George Porter
Deposited On:10 Aug 2020 16:25
Last Modified:16 Nov 2021 18:35

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