Format

Send to

Choose Destination
J Cell Biol. 2018 Apr 2;217(4):1217-1231. doi: 10.1083/jcb.201605106. Epub 2018 Mar 1.

An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly.

Author information

1
Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, AZ.
2
National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD.
3
Department of Biochemistry and Biophysics, Program in Molecular and Cellular Biophysics, University of North Carolina, Chapel Hill, NC.
4
Department of Biology, University of North Carolina, Chapel Hill, NC.
5
Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, AZ gcrogers@email.arizona.edu.

Abstract

Polo-like kinase 4 (Plk4) initiates an early step in centriole assembly by phosphorylating Ana2/STIL, a structural component of the procentriole. Here, we show that Plk4 binding to the central coiled-coil (CC) of Ana2 is a conserved event involving Polo-box 3 and a previously unidentified putative CC located adjacent to the kinase domain. Ana2 is then phosphorylated along its length. Previous studies showed that Plk4 phosphorylates the C-terminal STil/ANa2 (STAN) domain of Ana2/STIL, triggering binding and recruitment of the cartwheel protein Sas6 to the procentriole assembly site. However, the physiological relevance of N-terminal phosphorylation was unknown. We found that Plk4 first phosphorylates the extreme N terminus of Ana2, which is critical for subsequent STAN domain modification. Phosphorylation of the central region then breaks the Plk4-Ana2 interaction. This phosphorylation pattern is important for centriole assembly and integrity because replacement of endogenous Ana2 with phospho-Ana2 mutants disrupts distinct steps in Ana2 function and inhibits centriole duplication.

PMID:
29496738
PMCID:
PMC5881488
DOI:
10.1083/jcb.201605106
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center