Résumé
Cadherins are essential in many fundamental processes and assemble at regions of cell-cell contact in large macromolecular complexes named adherens junctions. Here, we identified Flotillin 1 and 2 as new partners of the Cadherin complexes. We show that Flotillins are localized at cell-cell junctions (CCJ) in a Cadherin-dependent manner. Flotillins and Cadherins are constitutively associated at the plasma membrane and their colocalization at CCJ increases with CCJ maturation. Using 3D-SIM super-resolution microscopy, we demonstrate that Cadherins and Flotillins complexes are associated with F-actin bundles at CCJ. The knockdown of Flotillins dramatically affected N- and E-cadherin recruitment at CCJ in mesenchymal and epithelial cell types and perturbed CCJ integrity and functionality. Moreover, we show that Flotillins are required for Cadherin association with GM1-containing plasma membrane micro-domains. This allows p120 Catenin binding to the Cadherin complex and its stabilization at CCJ. Altogether, these data demonstrate that Flotillin micro-domains are required for Cadherin stabilization at CCJ and for the formation of functional CCJ.