2. Academic Validation
  3. Phosphorylation by Aurora kinase A facilitates cortical-cytoplasmic dynamics of Par-3 in asymmetric division of radial glia progenitors

Phosphorylation by Aurora kinase A facilitates cortical-cytoplasmic dynamics of Par-3 in asymmetric division of radial glia progenitors

  • Sci Adv. 2025 May 16;11(20):eadq3858. doi: 10.1126/sciadv.adq3858.
Jason Q Garcia 1 2,  Vincent Mouilleau 1,  Henry Ng 2 3,  Xiang Zhao 1 4,  David O Morgan 2 3,  Su Guo 1 2 5
Affiliations

Affiliations

  • 1 Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 2 Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 3 Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 4 Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • 5 Programs in Biological Sciences and Quantitative Biosciences, Institute of Human Genetics, Kavli Institute for Fundamental Neuroscience, Bakar Aging Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
PMID: 40367180 DOI: 10.1126/sciadv.adq3858
Abstract

During asymmetric cell division (ACD) of radial glia progenitors (RGPs), the cortical polarity regulator Par-3 is detected in the cytoplasm colocalizing with dynein and Notch ligand DeltaD (Dld). What drives Par-3 to the cytoplasm and its impact on RGP ACD remain unknown. Here, we visualize cytoplasmic Par-3 using in vivo time-lapse imaging and find that Ser954 of zebrafish Par-3 is phosphorylated by Aurora Kinase A (AurkA) in vitro. Expression of the nonphosphorylated mutant Par-3S954A dominant negatively affects embryonic development, reduces cytoplasmic Par-3, and disrupts the anteroposterior asymmetry of cortical Par-3 and Dld endosomes and, in turn, daughter cell fate. AurkA in mitotic RGPs shows dynamic pericentrosomal distribution that transiently colocalizes with cortical Par-3 preferentially on the posterior side. AurkA is both necessary and sufficient to increase cytoplasmic while decreasing cortical Par-3, disrupts Par-3 cortical asymmetry, and perturbs polarized Dld endosome dynamics. These findings suggest that AurkA regulates Par-3 cortical-cytoplasmic dynamics that is critical for ACD and daughter cell fate.

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