Think Globally, Act Locally
The transduction of mechanical stimuli to alter intracellular biochemistry contributes to the regulation of intercellular adhesion, tissue barrier integrity, cell shape, and organ size. We previously demonstrated that cadherin complexes—principle adhesion proteins at cell-cell junctions in all tissues—transduce mechanical perturbations at intercellular junctions. Cadherin-based force transduction actuates proximal cytoskeletal remodeling and adhesion reinforcement. Initial findings identified alpha catenin, a cytoplasmic protein that couples cadherin to actin, as the principle force transducer in these complexes, but the latter mechanism focused solely on local cytoskeletal changes. Here we present evidence for an additional, parallel cadherin-mediated mechanotransduction pathway that actuates global signals, which remodel focal adhesions and regulate global cell mechanics. We identified the principle effectors in this pathway, which integrates cadherin force transduction and integrins within a global mechanosensitive, signaling network. Moreover, these signals propagate through tissues to disrupt intercellular junctions far from the mechanical stimulus. Together these studies reveal the capacity of local perturbations to alter global tissue functions through this integrated, force transduction network.