title: Flotillin microdomains stabilize cadherins at cell-cell junctions.
abstract: Cadherins are essential in many fundamental processes and assemble at regions of cell-cell contact in large macromolecular complexes named adherens junctions. We have identified flotillin 1 and 2 as new partners of the cadherin complexes. We show that flotillins are localised at cell-cell junctions (CCJs) in a cadherin-dependent manner. Flotillins and cadherins are constitutively associated at the plasma membrane and their colocalisation at CCJ increases with CCJ maturation. Using three-dimensional structured illumination super-resolution microscopy, we found that cadherin and flotillin complexes are associated with F-actin bundles at CCJs. The knockdown of flotillins dramatically affected N- and E-cadherin recruitment at CCJs in mesenchymal and epithelial cell types and perturbed CCJ integrity and functionality. Moreover, we determined that flotillins are required for cadherin association with GM1-containing plasma membrane microdomains. This allows p120 catenin binding to the cadherin complex and its stabilization at CCJs. Altogether, these data demonstrate that flotillin microdomains are required for cadherin stabilization at CCJs and for the formation of functional CCJs.
authors.affiliation: Equipe Labellisée Ligue Contre le Cancer, Universités Montpellier 2 et 1, CRBM, CNRS, UMR 5237, 1919 Route de Mende, 34293 Montpellier, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Guillaume
authors.forename: Franck
authors.initials: F
authors.lastname: Comunale
authors.forename: Nam
authors.initials: N
authors.lastname: Do Khoa
authors.forename: Damien
authors.initials: D
authors.lastname: Planchon
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bodin
authors.forename: Cécile
authors.initials: C
authors.lastname: Gauthier-Rouvière
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D007365:Intercellular Junctions / Q000235:genetics* / Q000378:metabolism; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D049128:Sphingolipid Activator Proteins / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D008565:Membrane Proteins; D049128:Sphingolipid Activator Proteins; C106354:flotillins; D000095002:Delta Catenin; C000722347:CTNND1 protein, human
keywords: Cadherins; Cell–cell junctions; Flotillins