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A CDK1 phosphorylation site on Drosophila PAR-3 regulates neuroblast polarisation and sensory organ formation.

Nicolas Loyer | Elizabeth K J Hogg | Hayley G Shaw | Anna Pasztor | David H Murray | Greg M Findlay | Jens Januschke
eLife | 2024

The generation of distinct cell fates during development depends on asymmetric cell division of progenitor cells. In the central and peripheral nervous system of Drosophila, progenitor cells respectively called neuroblasts or sensory organ precursors use PAR polarity during mitosis to control cell fate determination in their daughter cells. How polarity and the cell cycle are coupled, and how the cell cycle machinery regulates PAR protein function and cell fate determination is poorly understood. Here, we generate an analog sensitive allele of CDK1 and reveal that its partial inhibition weakens but does not abolish apical polarity in embryonic and larval neuroblasts and leads to defects in polarisation of fate determinants. We describe a novel in vivo phosphorylation of Bazooka, the Drosophila homolog of PAR-3, on Serine180, a consensus CDK phosphorylation site. In some tissular contexts, phosphorylation of Serine180 occurs in asymmetrically dividing cells but not in their symmetrically dividing neighbours. In neuroblasts, Serine180 phosphomutants disrupt the timing of basal polarisation. Serine180 phosphomutants also affect the specification and binary cell fate determination of sensory organ precursors as well as Baz localisation during their asymmetric cell divisions. Finally, we show that CDK1 phosphorylates Serine-S180 and an equivalent Serine on human PAR-3 in vitro.

Pubmed ID: 38869055

Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 10.35802/211209
  • Agency: Wellcome Trust, United Kingdom
    Id: 211193/Z/18/Z
  • Agency: NIH HHS, United States
    Id: P40 OD018537
  • Agency: Wellcome Trust, United Kingdom
    Id: 211209/Z/18/7
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/V001353/1
  • Agency: Wellcome Trust, United Kingdom
    Id: 100031/Z/12/A
  • Agency: Royal Society,
    Id: RGS/R2/180284
  • Agency: Wellcome Trust, United Kingdom
    Id: 10.35802/100031
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/T017546/1
  • Agency: Wellcome Trust, United Kingdom
    Id: 10.35802/211193

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