De novo E-cadherin/catenin complex formation controls basal epithelial mechanics and force transmission for apoptotic cell clearance.

Abstract

Beyond serving as cohesive barriers, epithelia clear apoptotic cells to regulate development, homeostasis and inflammation. How epithelial cells remodel their shape during phagocytosis while preserving tissue integrity, and the role of adhesion receptors in this process, remain unclear. Using live in vivo imaging of phagocyte-target interactions in zebrafish (Danio rerio) embryos, we show that basal and apical epithelial domains are mechanically decoupled, enabling engulfment without disrupting tissue cohesion. We identify a dynamic assembly of E-cadherin/catenin complexes at the basal epithelial surface in contact with apoptotic cells. Targeted perturbations reveal two critical functions of de novo E-cadherin/catenin complex formation at the phagocytic synapse: α-catenin acts as a physical linker transmitting actin-generated forces required for engulfment, while p120-catenin restrains Myosin II activity, enabling efficient clearance. We further demonstrate the conservation of E-cadherin-dependent apoptotic cell clearance in the mouse trophectoderm. These findings reveal that the E-cadherin/catenin complex is repurposed at the phagocytic synapse as a mechano-regulator of epithelial efferocytosis beyond its canonical role in tissue cohesion.