Cadherin regulation of endoplasmic reticulum-plasma membrane contact sites

The spatial organization and dynamics of the endoplasmic reticulum (ER) govern when and where ER tubules engage with other organelles and the plasma membrane. We previously found that ER tubules are closely associated with desmosomes, but the mechanisms of ER recruitment to these adhesive intercellular junctions were unclear. Here, we demonstrate that recruitment of ER tubules to intercellular junctions is dependent upon E-cadherin association with α-catenin. During junction formation, adherens junctions and ER tubules appear nearly simultaneously at nascent cell-cell contacts, followed by desmosome formation. ER recruitment allows the formation of ER-plasma membrane contact sites (ER-PMCSs) and an assembly comprising adherens junctions, ER-PMCS, and desmosomes. Ablating adherens junctions disrupts this tripartite assembly and perturbs global lipid levels. Collectively, our findings identify cadherins as key organizers of ER-PMCS positioning and suggest that the cell-cell adhesion-organelle unit integrates cellular mechanical elements with plasma membrane homeostasis.