A CDK1 phosphorylation site on Drosophila PAR-3 regulates neuroblast polarisation and sensory organ formation
- University of Dundee, United Kingdom
Abstract
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.
Data availability
The raw western blot data shown in figure 7 are available in figure 7 supplement.The mass spectrometry proteomics data presented in figure 7 have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD051560.
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Funding
Wellcome Trust (100031/Z/12/A)
- Jens Januschke
Wellcome Trust (211193/Z/18/Z)
- David H Murray
Wellcome Trust (211209/Z/18/7)
- Greg M Findlay
Biotechnology and Biological Sciences Research Council (BB/V001353/1)
- Jens Januschke
Royal Society (RGS/R2/180284)
- David H Murray
Biotechnology and Biological Sciences Research Council (BB/T017546/1)
- Jens Januschke
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2024, Loyer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A CDK1 phosphorylation site on Drosophila PAR-3 regulates neuroblast polarisation and sensory organ formation
eLife 13:e97902.
https://doi.org/10.7554/eLife.97902
