
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.06.611639
preprint
1
Article
α-catenin phosphorylation is elevated during mitosis to resist apical rounding and epithelial barrier leak
Le Phuong M http://orcid.org/0009-0008-0822-6668

Quinn Jeanne M http://orcid.org/0000-0002-7830-4659

Steffeck Adam WT http://orcid.org/0000-0002-5660-9371

Flozak Annette S
Huang Che-Fan http://orcid.org/0000-0002-5799-1533

Gottardi Cara J http://orcid.org/0000-0003-0912-7617

06 9 2024
2024.09.06.611639https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.06.611639
nihpp-2024.09.06.611639.pdf
Epithelial cell cohesion and barrier function critically depend on α-catenin, an actin-binding protein and essential constituent of cadherin-catenin-based adherens junctions. α-catenin undergoes actomyosin force-dependent unfolding of both actin-binding and middle domains to strongly engage actin filaments and its various effectors, where this mechanosensitivity is critical for adherens junction function. We previously showed that α-catenin is highly phosphorylated in an unstructured region that links mechanosensitive middle- and actin-binding domains (known as the P-linker region), but the cellular processes that promote α-catenin phosphorylation have remained elusive. Here, we leverage a previously published phospho-proteomic data set to show that the α-catenin P-linker region is maximally phosphorylated during mitosis. By reconstituting α-catenin Crispr KO MDCK with wild-type, phospho-mutant and mimic forms of α-catenin, we show that full phosphorylation restrains mitotic cell rounding in the apical direction, strengthening interactions between dividing and non-dividing neighbors to limit epithelial barrier leak. Since major scaffold components of adherens junctions, tight junctions and desmosomes are also differentially phosphorylated during mitosis, we reason that epithelial cell division may be a tractable system to understand how junction complexes are coordinately regulated to sustain barrier function under tension-generating morphogenetic processes.
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pmc
