Multivalent Afadin Interaction Promotes IDR-Mediated Condensate Formation and Junctional Separation of Epithelial Cells

Summary In epithelial cells, cell-cell adhesion is mediated by the apical junctional complex (AJC), which consists of tight junctions (TJs) and adherens junctions (AJs) aligned from the apical to the basal axis. However, the mechanism of AJC formation on the apical side and the separation of these junctions within AJCs are poorly understood. We found that multivalent interactions of afadin with adhesion molecules and the cytoskeleton lead to condensate formation in an intrinsically disordered region (IDR)-dependent manner, which promotes efficient accumulation in the linear AJ during initial junction formation. Furthermore, we found that afadin and ZO-1 were able to induce different condensate formations in the cell and that these molecules were differentially distributed from each other. These properties of afadin explain how it strictly localizes to AJs in epithelial cells and is involved in regulating the segregation of AJ and TJ within the AJC.