PLK4 trans-Autoactivation Controls Centriole Biogenesis in Space

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.

Descrição

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Palavras-chave

Animals Centrioles Centrosome Drosophila Proteins Drosophila melanogaster Gene Expression Regulation, Developmental Peroxisomes Phosphorylation Protein-Serine-Threonine Kinases Spermatogenesis

URI

http://hdl.handle.net/10400.7/830

Citação

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 Bettencourt-Dias, PLK4 trans-Autoactivation Controls Centriole Biogenesis in Space, Developmental Cell, Volume 35, Issue 2, 2015, Pages 222-235, ISSN 1534-5807, https://doi.org/10.1016/j.devcel.2015.09.020. (http://www.sciencedirect.com/science/article/pii/S1534580715006218)