Abstract
Epithelial cell cohesion and barrier function critically depend on αα<math><mrow><mtext>α</mtext></mrow> </math> -catenin, an actin-binding protein and essential constituent of cadherin-catenin-based adherens junctions. αα<math><mrow><mtext>α</mtext></mrow> </math> -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 αα<math><mrow><mtext>α</mtext></mrow> </math> -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 αα<math><mrow><mtext>α</mtext></mrow> </math> -catenin phosphorylation have remained elusive. Here, we leverage a previously published phosphor-proteomic data set to show that the αα<math><mrow><mtext>α</mtext></mrow> </math> -catenin P-linker region is maximally phosphorylated during mitosis. By reconstituting αα<math><mrow><mtext>α</mtext></mrow> </math> -catenin Crispr KO MDCK with wild-type, phospho- mutant and mimic forms of αα<math><mrow><mtext>α</mtext></mrow> </math> -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.