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EMBO Rep. 2016 Mar;17(3):326-37. doi: 10.15252/embr.201541432. Epub 2016 Jan 11.

A non-canonical function of Plk4 in centriolar satellite integrity and ciliogenesis through PCM1 phosphorylation.

Author information

1
The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, UK Developmental Biomedical Science, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Ikoma Nara, Japan.
2
The Francis Crick Institute, Clare Hall Laboratory, London, UK.
3
The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, UK Hiroshima Research Center for Healthy Aging (HiHA), Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter Hiroshima University, Higashi-Hiroshima, Japan takashi-toda@hiroshima-u.ac.jp.

Abstract

Centrioles are the major constituents of the animal centrosome, in which Plk4 kinase serves as a master regulator of the duplication cycle. Many eukaryotes also contain numerous peripheral particles known as centriolar satellites. While centriolar satellites aid centriole assembly and primary cilium formation, it is unknown whether Plk4 plays any regulatory roles in centriolar satellite integrity. Here we show that Plk4 is a critical determinant of centriolar satellite organisation. Plk4 depletion leads to the dispersion of centriolar satellites and perturbed ciliogenesis. Plk4 interacts with the satellite component PCM1, and its kinase activity is required for phosphorylation of the conserved S372. The nonphosphorylatable PCM1 mutant recapitulates phenotypes of Plk4 depletion, while the phosphomimetic mutant partially rescues the dispersed centriolar satellite patterns and ciliogenesis in cells depleted of PCM1. We show that S372 phosphorylation occurs during the G1 phase of the cell cycle and is important for PCM1 dimerisation and interaction with other satellite components. Our findings reveal that Plk4 is required for centriolar satellite function, which may underlie the ciliogenesis defects caused by Plk4 dysfunction.

KEYWORDS:

PCM1; Plk4; centriolar satellites; centrosome; ciliogenesis

PMID:
26755742
PMCID:
PMC4772974
DOI:
10.15252/embr.201541432
[Indexed for MEDLINE]
Free PMC Article

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