title: α-Catenin and vinculin cooperate to promote high E-cadherin-based adhesion strength.
abstract: Maintaining cell cohesiveness within tissues requires that intercellular adhesions develop sufficient strength to support traction forces applied by myosin motors and by neighboring cells. Cadherins are transmembrane receptors that mediate intercellular adhesion. The cadherin cytoplasmic domain recruits several partners, including catenins and vinculin, at sites of cell-cell adhesion. Our study used force measurements to address the role of αE-catenin and vinculin in the regulation of the strength of E-cadherin-based adhesion. αE-catenin-deficient cells display only weak aggregation and fail to strengthen intercellular adhesion over time, a process rescued by the expression of αE-catenin or chimeric E-cadherin·αE-catenins, including a chimera lacking the αE-catenin dimerization domain. Interestingly, an αE-catenin mutant lacking the modulation and actin-binding domains restores cadherin-dependent cell-cell contacts but cannot strengthen intercellular adhesion. The expression of αE-catenin mutated in its vinculin-binding site is defective in its ability to rescue cadherin-based adhesion strength in cells lacking αE-catenin. Vinculin depletion or the overexpression of the αE-catenin modulation domain strongly decreases E-cadherin-mediated adhesion strength. This supports the notion that both molecules are required for intercellular contact maturation. Furthermore, stretching of cell doublets increases vinculin recruitment and α18 anti-αE-catenin conformational epitope immunostaining at cell-cell contacts. Taken together, our results indicate that αE-catenin and vinculin cooperatively support intercellular adhesion strengthening, probably via a mechanoresponsive link between the E-cadherin·β-catenin complexes and the underlying actin cytoskeleton.
authors.affiliation: Department of Natural Sciences, Colby-Sawyer College, New London, New Hampshire 03257, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Thomas
authors.forename: Cécile
authors.initials: C
authors.lastname: Boscher
authors.forename: Yeh-Shiu
authors.initials: YS
authors.lastname: Chu
authors.forename: Damien
authors.initials: D
authors.lastname: Cuvelier
authors.forename: Clara
authors.initials: C
authors.lastname: Martinez-Rico
authors.forename: Rima
authors.initials: R
authors.lastname: Seddiki
authors.forename: Julie
authors.initials: J
authors.lastname: Heysch
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Thiery
authors.forename: René-Marc
authors.initials: RM
authors.lastname: Mege
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dufour
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D011485:Protein Binding; D013997:Time Factors; D016596:Vinculin / Q000378:metabolism*; D051178:alpha Catenin / Q000378:metabolism*
chemical_list: D000199:Actins; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051178:alpha Catenin; D016596:Vinculin