title: Reevaluating αE-catenin monomer and homodimer functions by characterizing E-cadherin/αE-catenin chimeras.
abstract: As part of the E-cadherin-β-catenin-αE-catenin complex (CCC), mammalian αE-catenin binds F-actin weakly in the absence of force, whereas cytosolic αE-catenin forms a homodimer that interacts more strongly with F-actin. It has been concluded that cytosolic αE-catenin homodimer is not important for intercellular adhesion because E-cadherin/αE-catenin chimeras thought to mimic the CCC are sufficient to induce cell-cell adhesion. We show that, unlike αE-catenin in the CCC, these chimeras homodimerize, bind F-actin strongly, and inhibit the Arp2/3 complex, all of which are properties of the αE-catenin homodimer. To more accurately mimic the junctional CCC, we designed a constitutively monomeric chimera, and show that E-cadherin-dependent cell adhesion is weaker in cells expressing this chimera compared with cells in which αE-catenin homodimers are present. Our results demonstrate that E-cadherin/αE-catenin chimeras used previously do not mimic αE-catenin in the native CCC, and imply that both CCC-bound monomer and cytosolic homodimer αE-catenin are required for strong cell-cell adhesion.
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Bianchini
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305.
authors.forename: Khameeka N
authors.initials: KN
authors.lastname: Kitt
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305.
authors.forename: Martijn
authors.initials: M
authors.lastname: Gloerich
authors.affiliation: Department of Structural Biology, Stanford University, Stanford, CA 94305.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pokutta
authors.affiliation: Department of Structural Biology, Stanford University, Stanford, CA 94305 Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.
authors.forename: William I
authors.initials: WI
authors.lastname: Weis
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305 Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305 wjnelson@stanford.edu.
authors.forename: W James
authors.initials: WJ
authors.lastname: Nelson
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D007739:L Cells; D051379:Mice; D011485:Protein Binding / Q000502:physiology; D055503:Protein Multimerization / Q000502:physiology*; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D015820:Cadherins; C495272:Ctnna1 protein, mouse; D051178:alpha Catenin