PLK4 trans-Autoactivation Controls Centriole Biogenesis in Space

• DOI: 10.1016/j.devcel.2015.09.020
• Publication Date: 2015-10-23T08:42:52Z
• Authors: Carla A.M. Lopes; Swadhin Chandra Jana; Inês Cunha-Ferreira; Sihem Zitouni; Inês Bento; Paulo Duarte; Samuel Gilberto; Francisco Freixo; Adán Guerrero; Maria Francia; Mariana Lince-Faria; Jorge Carneiro; Mónica Bettencour...
• Keywords: Centrosome; 0301 basic medicine; 0303 health sciences; Gene Expression Regulation, Developmental; Protein Serine-Threonine Kinases; Protein-Serine-Threonine Kinases; 3. Good health; 03 medical and health sciences; Drosophila melanogaster; Peroxisomes; Animals; Drosophila Proteins; Phosphorylation; Spermatogenesis; Developmental Biology; Centrioles

Centrioles are essential for cilia and centrosome assembly. In centriole-containing cells, centrioles always form juxtaposed to pre-existing ones, motivating a century-old debate on centriole biogenesis control. Here, we show that trans-autoactivation of Polo-like kinase 4 (PLK4), the trigger of centriole biogenesis, is a critical event in the spatial control of that process. We demonstrate that centrioles promote PLK4 activation through its recruitment and local accumulation. Though centriole removal reduces the proportion of active PLK4, this is rescued by concentrating PLK4 to the peroxisome lumen. Moreover, while mild overexpression of PLK4 only triggers centriole amplification at the existing centriole, higher PLK4 levels trigger both centriolar and cytoplasmatic (de novo) biogenesis. Hence, centrioles promote their assembly locally and disfavor de novo synthesis. Similar mechanisms enforcing the local concentration and/or activity of other centriole components are likely to contribute to the spatial control of centriole biogenesis under physiological conditions.