PLK4 promotes centriole duplication by phosphorylating STIL to link the procentriole cartwheel to the microtubule wall

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Abstract

Centrioles play critical roles in organizing the assembly of the mitotic spindle and templating the formation of primary cilia. Centriole duplication occurs once per cell cycle and is regulated by Polo-like kinase 4 (PLK4). Although significant progress has been made in understanding centriole composition, we have limited knowledge of how PLK4 activity controls specific steps in centriole formation. Here we show that PLK4 phosphorylates its centriole substrate STIL on a conserved site, S428, to promote STIL binding to CPAP. This phospho-dependent binding interaction is conserved in Drosophila and facilitates the stable incorporation of both STIL and CPAP into the centriole. We propose that procentriole assembly requires PLK4 to phosphorylate STIL in two different regions: phosphorylation of residues in the STAN motif allow STIL to bind SAS6 and initiate cartwheel assembly, while phosphorylation of S428 promotes the binding of STIL to CPAP, linking the cartwheel to microtubules of the centriole wall.

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We have included a source file for all the statistical tests performed. Source data for all of the figures is provided in the 'Source Data' table.

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Tyler Chistopher Moyer

Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Andrew Jon Holland

Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States

For correspondence
aholland@jhmi.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3728-6367

Funding

National Institutes of Health (R01GM114119)

Andrew Jon Holland

American Cancer Society (RSG-16-156-01-CCG)

Andrew Jon Holland

National Institutes of Health (T32GM007445)

Tyler Chistopher Moyer

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.