Affiliation:
1. Instituto Gulbenkian de Ciência, Oeiras, Portugal
2. National Centre for Biological Sciences, Bangalore, India
Abstract
Centrioles form centrosomes and cilia. In most proliferating cells, centrioles assemble through canonical duplication, which is spatially, temporally, and numerically regulated by the cell cycle and the presence of mature centrioles. However, in certain cell types, centrioles assemble de novo, yet by poorly understood mechanisms. Herein, we established a controlled system to investigate de novo centriole biogenesis, using Drosophila melanogaster egg explants overexpressing Polo-like kinase 4 (Plk4), a trigger for centriole biogenesis. We show that at a high Plk4 concentration, centrioles form de novo, mature, and duplicate, independently of cell cycle progression and of the presence of other centrioles. Plk4 concentration determines the temporal onset of centriole assembly. Moreover, our results suggest that distinct biochemical kinetics regulate de novo and canonical biogenesis. Finally, we investigated which other factors modulate de novo centriole assembly and found that proteins of the pericentriolar material (PCM), and in particular γ-tubulin, promote biogenesis, likely by locally concentrating critical components.
Funder
National Portuguese funding
Lisboa Regional Operational Program
Lisboa 2020
Portugal 2020 Agreement
European Regional Development Fund
Congento
Bloomington Drosophila Stock Center
Boehringer Ingelheim Fonds
Human Frontiers Science Program
Fundação para a Ciência e a Tecnologia
Calouste Gulbenkian Foundation
EMBO
National Centre for Biological Sciences
DST
Government of India
Max Planck Lipid Centre
The Wellcome Trust DBT India Alliance
European Commission FP7
European Research Council
Publisher
Rockefeller University Press