α-Catenin phosphorylation determines adhesion strength

Adherens junctions, mediated by cadherin–catenin complexes (CCCs), form between cells and are crucial for epithelial tissue homeostasis and collective cell behaviour during development. However, it is not well understood how CCCs are regulated and what defines adhesion strength at the molecular level. In this study (p. 1150), Ulrich Tepass, Cara Gottardi and co-workers set out to define phosphorylation sites in α-catenin using affinity-purified αE-catenin-containing complexes from human cells. They identify a major evolutionarily conserved phospho-domain in αE-catenin that they term the phospho-linker (P-linker); this is the main phosphorylated region of α-catenin in cells and is sequentially modified by casein kinase 2 and 1. Although phosphorylation at these sites is not required for basal CCC assembly, it might be necessary to support mechanically resistant adhesions in vivo, as Drosophila expressing P-linker mutants show reduced viability. With regard to the underlying mechanism, their data suggest that phosphorylation can alter the conformation of αE-catenin, which could be important when the junction is under tension. In addition, analysis of nonphosphorylatable and phosphomimetic forms of α-catenin point to the importance of dynamic α-catenin phosphorylation in the assembly of fully functional CCCs that are required for epithelial integrity. These findings also suggest a means to reinforce CCC function under conditions in which cell–cell adhesion is disturbed.