4.8 Article

Centrioles generate a local pulse of Polo/PLK1 activity to initiate mitotic centrosome assembly

Journal

EMBO JOURNAL
Volume 41, Issue 11, Pages -

Publisher

WILEY
DOI: 10.15252/embj.2022110891

Keywords

cell cycle; centrosome; oscillator; PCM; PLK1

Funding

  1. Wellcome Trust [107457, 215523]
  2. EPSRC [EP/R020205/1]
  3. John Fell Fund Award
  4. CRUK Oxford Centre Prize [C5255/A23225]
  5. Balliol Jason Hu Scholarship
  6. Clarendon Scholarship

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Mitotic centrosomes are formed through the recruitment of pericentriolar material (PCM) around centrioles, and Polo/PLK1 protein kinase is essential for this process. The level of Polo in centrosomes fluctuates during centrosome assembly, and a local pulse of Polo activity generated by interaction with its centriole receptor Ana1 (CEP295 in humans) could explain the dynamics of PCM scaffold assembly. This suggests that centrioles initiate centrosome maturation by generating a pulse of Polo activity before mitotic entry.
Mitotic centrosomes are formed when centrioles start to recruit large amounts of pericentriolar material (PCM) around themselves in preparation for mitosis. This centrosome maturation requires the centrioles and also Polo/PLK1 protein kinase. The PCM comprises several hundred proteins and, in Drosophila, Polo cooperates with the conserved centrosome proteins Spd-2/CEP192 and Cnn/CDK5RAP2 to assemble a PCM scaffold around the mother centriole that then recruits other PCM client proteins. We show here that in Drosophila syncytial blastoderm embryos, centrosomal Polo levels rise and fall during the assembly process-peaking, and then starting to decline, even as levels of the PCM scaffold continue to rise and plateau. Experiments and mathematical modelling indicate that a centriolar pulse of Polo activity, potentially generated by the interaction between Polo and its centriole receptor Ana1 (CEP295 in humans), could explain these unexpected scaffold assembly dynamics. We propose that centrioles generate a local pulse of Polo activity prior to mitotic entry to initiate centrosome maturation, explaining why centrioles and Polo/PLK1 are normally essential for this process.

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