title: The formation of ordered nanoclusters controls cadherin anchoring to actin and cell-cell contact fluidity.
abstract: Oligomerization of cadherins could provide the stability to ensure tissue cohesion. Cadherins mediate cell-cell adhesion by forming trans-interactions. They form cis-interactions whose role could be essential to stabilize intercellular junctions by shifting cadherin clusters from a fluid to an ordered phase. However, no evidence has been provided so far for cadherin oligomerization in cellulo and for its impact on cell-cell contact stability. Visualizing single cadherins within cell membrane at a nanometric resolution, we show that E-cadherins arrange in ordered clusters, providing the first demonstration of the existence of oligomeric cadherins at cell-cell contacts. Studying the consequences of the disruption of the cis-interface, we show that it is not essential for adherens junction formation. Its disruption, however, increased the mobility of junctional E-cadherin. This destabilization strongly affected E-cadherin anchoring to actin and cell-cell rearrangement during collective cell migration, indicating that the formation of oligomeric clusters controls the anchoring of cadherin to actin and cell-cell contact fluidity.
authors.affiliation: Institut Jacques Monod, Centre National de la Recherche Scientifique, Université Paris Diderot, 75205 Paris, France Mechanobiology Institute, University of Singapore, Singapore 117411, Singapore.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Strale
authors.affiliation: Institut Jacques Monod, Centre National de la Recherche Scientifique, Université Paris Diderot, 75205 Paris, France Institut de Génétique et Développement de Rennes, Centre National de la Recherche Scientifique, Université de Rennes 1, 35042 Rennes, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Duchesne
authors.affiliation: Institut Jacques Monod, Centre National de la Recherche Scientifique, Université Paris Diderot, 75205 Paris, France.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Peyret
authors.affiliation: Laboratoire Matière et Systèmes Complexes, Centre National de la Recherche Scientifique, Université Paris Diderot, 75205 Paris, France.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Montel
authors.affiliation: Institut Jacques Monod, Centre National de la Recherche Scientifique, Université Paris Diderot, 75205 Paris, France.
authors.forename: Thao
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Institut Jacques Monod, Centre National de la Recherche Scientifique, Université Paris Diderot, 75205 Paris, France Ocular Surface Research Group, Singapore Eye Research Institute, Singapore 169856, Singapore.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Png
authors.affiliation: Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, D-60438 Frankfurt, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Tampé
authors.affiliation: Northwestern University, Chicago, Il 60208.
authors.forename: Sergey
authors.initials: S
authors.lastname: Troyanovsky
authors.affiliation: Laboratoire Matière et Systèmes Complexes, Centre National de la Recherche Scientifique, Université Paris Diderot, 75205 Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hénon
authors.affiliation: Institut Jacques Monod, Centre National de la Recherche Scientifique, Université Paris Diderot, 75205 Paris, France Mechanobiology Institute, University of Singapore, Singapore 117411, Singapore.
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
authors.affiliation: Institut Jacques Monod, Centre National de la Recherche Scientifique, Université Paris Diderot, 75205 Paris, France rene-marc.mege@ijm.fr.
authors.forename: René-Marc
authors.initials: RM
authors.lastname: Mège
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D022005:Adherens Junctions / Q000378:metabolism; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins