Title: Plk4 Phosphorylates Ana2 to Trigger Sas6 Recruitment and Procentriole Formation
Abstract: Centrioles are 9-fold symmetrical structures at the core of centrosomes and base of cilia whose dysfunction has been linked to a wide range of inherited diseases and cancer [1Nigg E.A. Raff J.W. Centrioles, centrosomes, and cilia in health and disease.Cell. 2009; 139: 663-678Abstract Full Text Full Text PDF PubMed Scopus (683) Google Scholar]. Their duplication is regulated by a protein kinase of conserved structure, the C. elegans ZYG-1 or its Polo-like kinase 4 (Plk4) counterpart in other organisms [2O'Connell K.F. Caron C. Kopish K.R. Hurd D.D. Kemphues K.J. Li Y. White J.G. The C. elegans zyg-1 gene encodes a regulator of centrosome duplication with distinct maternal and paternal roles in the embryo.Cell. 2001; 105: 547-558Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar, 3Habedanck R. Stierhof Y.D. Wilkinson C.J. Nigg E.A. The Polo kinase Plk4 functions in centriole duplication.Nat. Cell Biol. 2005; 7: 1140-1146Crossref PubMed Scopus (612) Google Scholar, 4Bettencourt-Dias M. Rodrigues-Martins A. Carpenter L. Riparbelli M. Lehmann L. Gatt M.K. Carmo N. Balloux F. Callaini G. Glover D.M. SAK/PLK4 is required for centriole duplication and flagella development.Curr. Biol. 2005; 15: 2199-2207Abstract Full Text Full Text PDF PubMed Scopus (444) Google Scholar]. Although Plk4's centriolar partners and mechanisms that regulate its stability are known, its crucial substrates for centriole duplication have never been identified. Here we show that Drosophila Plk4 phosphorylates four conserved serines in the STAN motif of the core centriole protein Ana2 to enable it to bind and recruit its Sas6 partner. Ana2 and Sas6 normally load onto both mother and daughter centrioles immediately after their disengagement toward the end of mitosis to seed procentriole formation. Nonphosphorylatable Ana2 still localizes to the centriole but can no longer recruit Sas6 and centriole duplication fails. Thus, following centriole disengagement, recruitment of Ana2 and its phosphorylation by Plk4 are the earliest known events in centriole duplication to recruit Sas6 and thereby establish the architecture of the new procentriole engaged with its parent.