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.
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Carla A M
CA
Lopes
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Swadhin Chandra
SC
Jana
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Inês
I
Cunha-Ferreira
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Sihem
S
Zitouni
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Inês
I
Bento
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Paulo
P
Duarte
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Samuel
S
Gilberto
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Francisco
F
Freixo
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Adán
A
Guerrero
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Maria
M
Francia
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Mariana
M
Lince-Faria
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Jorge
J
Carneiro
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal. Electronic address: mdias@igc.gulbenkian.pt.
Mónica
M
Bettencourt-Dias
D000818:Animals; D002502:Centrioles / Q000235:genetics* / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D020675:Peroxisomes / Q000235:genetics; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics*
D029721:Drosophila Proteins; D017346:Protein Serine-Threonine Kinases; C522064:Sak protein, Drosophila