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In a story published in the EMBO Journal, Wong, Wilmott et al. shed light on the mechanism of Polo action in the assembly of the centrosome.

Cell division is an essential function of cells, and appropriate partitioning of DNA and other cellular materials is critical for the daughter cells’ functioning and survival. In animals, this process is orchestrated by the centrosomes, structures which nucleate microtubules and assist with the division of materials. In a recent paper from the Raff lab, Wong, Wilmott et al. shed light on the mechanism by which protein kinase Polo/PLK1 helps to recruit a scaffold of ‘pericentriolar material’ (PCM) to the centrioles (around which centrosomes form), which helps assemble the centrosome during DNA synthesis.

Microscopic observation of syncytial blastoderm-stage Drosophila fly embryos (where initial rounds of nuclear divisions happen synchronously, making them easy to observe) showed that Polo recruitment to centrioles peaks and then falls during each synthesis cycle. Even as Polo levels drop, recruitment of scaffold material to the centrosome continues. Wong, Wilmott et al. hypothesised that a pulse of Polo activity might trigger assembly of the PCM matrix. In this scenario, protein Spd-2 is recruited at the centrioles and phosphorylated. This allows Spd-2 to form a weak scaffold which in turn recruits proteins Polo and Cnn, stabilising the scaffold. Polo phosphorylates Cnn, and phosphorylated Cnn in turn forms a stronger scaffold which continues to grow, and then plateaus. These observations were supported by mathematical modelling, which reproduced the unexpected phenomenon of Polo level reduction with concomitant scaffold expansion.

Wong, Wilmott et al. further confirmed that proteins Spd-2 and Ana1 are responsible for recruiting Polo and kickstarting this pulse of Polo activity. Intriguingly, old mother centrioles (which have been produced during a previous cycle, and so have some PCM remaining around them from the previous mitotic nuclear division) do not seem to have as great a requirement for Ana1, as the PCM itself can recruit Polo to aid its own expansion. However, both old and new mother centrioles appear to have a requirement for Spd-2, as Spd-2 recruits Polo to the PCM, unlike Ana1, which recruits Polo to the centrioles. These protein-protein dynamics were also confirmed via mathematical modelling.

This study sheds light on a fundamental biological process which still raises many interesting and important questions, as cell division and its (mis)regulation are hallmarks of various diseases, such as cancer.

Written by Alexandra Bisia (Robertson lab) @AlexandraBisia

Edited by Isabella Maudlin (Murphy lab) @BellaMaudlin

Article Title: Wong, Wilmott et al. (2022). Centrioles generate a local pulse of Polo/PLK1 activity to initiate mitotic centrosome assembly. EMBO Journal, 41:e110891 DOI:10.15252/embj.2022110891