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

Siu Shing Wong, Zachary M. Wilmott, Saroj Saurya, Ines Alvarez-Rodrigo, Felix Y. Zhou, Kwai Yin Chau, Alain Goriely, Jordan W. Raff

Research output: Contribution to journalArticlepeer-review

9 Citations (SciVal)

Abstract

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.

Original languageEnglish
Article numbere110891
JournalEMBO Journal
Volume41
Issue number11
Early online date3 May 2022
DOIs
Publication statusPublished - 1 Jun 2022
Externally publishedYes

Bibliographical note

Funding Information:
We are grateful to Stefano di Thalia (Duke University, USA) and Thomas Steinacker (Raff Lab) for communicating unpublished data, to Lisa Gartenmann for generating the Ubq‐NG‐Cnn line used in this study and to Alan Wainman for help with microscopy as part of the Micron Oxford Advanced Bioimaging Unit—partly funded by a Strategic Award from the Wellcome Trust (107457). We thank members of the Raff Laboratory for advice, discussion and for critically reading the manuscript. The research was funded by a Wellcome Trust Senior Investigator Award (215523) to JWR, an EPSRC award (EP/R020205/1) and a John Fell Fund Award to AG, and a CRUK Oxford Centre Prize DPhil Studentship (C5255/A23225), a Balliol Jason Hu Scholarship and a Clarendon Scholarship (to SSW).

Keywords

  • cell cycle
  • centrosome
  • oscillator
  • PCM
  • PLK1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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