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bioRxiv · 10.1101/2025.04.16.649205

Multivalent assembly of PAR-3/aPKC complexes establishes cell polarity in C. elegans zygotes

Hsu, S.-P.·Dickinson, D. J.
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Abstract

Cell polarity is essential for the formation and function of animal tissues. Atypical protein kinase C (aPKC), its cofactor PAR-6, and scaffold protein PAR-3 regulate cell polarity in many different animal cell types. PAR-3 oligomerization is important to establish cell polarity, but how oligomerization relates to the assembly of the PAR-3 / aPKC / PAR-6 complex is still unclear. Here, we use in vivo and ex vivo single molecule techniques to demonstrate cooperativity between PAR-3 oligomerization and its binding to aPKC / PAR-6 in the C. elegans zygote. Using genetic perturbations, we demonstrate that aPKC and PAR-6 have independent binding sites for PAR-3. We propose that multivalency drives cooperativity because a single aPKC / PAR-6 heterodimer can interact simultaneously with multiple PAR-3 molecules in an oligomer. Although single binding site mutations do not fully eliminate PAR-3 / aPKC / PAR-6 binding, they do abolish anterior-posterior polarity, demonstrating that PAR-3 / aPKC cooperativity is essential for polarity establishment. Finally, PAR-3 / aPKC cooperativity is downregulated in polarity maintenance, and this downregulation depends on the mitotic kinase PLK-1. Together, our results show how cells can developmentally regulate multivalent assembly of a key polarity complex to achieve timely segregation of cell fate determinants.

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Hsu, S.-P., Dickinson, D. J.. 2025-04-21. Multivalent assembly of PAR-3/aPKC complexes establishes cell polarity in C. elegans zygotes. https://doi.org/10.1101/2025.04.16.649205

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