797 Crosstalk between adherens junctions and desmosomes and associated cytoskeletons controls epidermal adhesion dynamics and mechanical resilience

The skin epidermis maintains a functional barrier while turning over and facing varying mechanical stresses. Adherens junctions (AJ) and desmosomes connect intercellular adhesion with the contractile actomyosin or mechanically resilient keratin cytoskeleton, respectively, to sense and respond to external and internal forces to preserve epidermal integrity. How these two systems crosstalk to coordinate self-renewing cell movement with mechanical barrier resilience is not known. To examine this, we combined knockout models, high end imaging, electron microscopy, force sensors and force measurements. We find that AJs through the actin-binding molecule a-catenin sense the contractile state of epithelial barriers, and resist this contractility through subsequent molecularly AJ reorganization, which is essential for the assembly and maturation of desmosomes. In contrast, desmosomes persist upon optogenetic disruption of adherens junctions, suggesting that desmosomes maintain cohesion when AJ reorganize to drive cell rearrangements. Finally, we find that keratins sense increased contractile prestress of stratified keratinocytes, and through reorganization mechanically balance this increase to maintain tissue integrity. Together, our data identify extensive molecular, cellular and supracellular crosstalk between AJs and desmosomes necessary for epidermal barrier dynamics and mechanical resilience.