title: Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex.
abstract: Calcium-dependent homotypic cell-cell adhesion, mediated by molecules such as E-cadherin, guides the establishment of classical epithelial cell polarity and contributes to the control of migration, growth, and differentiation. These actions involve additional proteins, including alpha- and beta-catenin (or plakoglobin) and p120, as well as linkage to the cortical actin cytoskeleton. The molecular basis for these interactions and their hierarchy of interaction remain controversial. We demonstrate a direct interaction between F-actin and alpha (E)-catenin, an activity not shared by either the cytoplasmic domain of E-cadherin or beta-catenin. Sedimentation assays and direct visualization by transmission electron microscopy reveal that alpha 1(E)-catenin binds and bundles F-actin in vitro with micromolar affinity at a catenin/G-actin monomer ratio of approximately 1:7 (mol/mol). Recombinant human beta-catenin can simultaneously bind to the alpha-catenin/actin complex but does not bind actin directly. Recombinant fragments encompassing the amino-terminal 228 residues of alpha 1(E)-catenin or the carboxyl-terminal 447 residues individually bind actin in cosedimentation assays with reduced affinity compared with the full-length protein, and neither fragment bundles actin. Except for similarities to vinculin, neither region contains sequences homologous to established actin-binding proteins. Collectively these data indicate that alpha 1 (E)-catenin is a novel actin-binding and -bundling protein and support a model in which alpha 1(E)-catenin is responsible for organizing and tethering actin filaments at the zones of E-cadherin-mediated cell-cell contact.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Rimm
authors.forename: E R
authors.initials: ER
authors.lastname: Koslov
authors.forename: P
authors.initials: P
authors.lastname: Kebriaei
authors.forename: C D
authors.initials: CD
authors.lastname: Cianci
authors.forename: J S
authors.initials: JS
authors.lastname: Morrow
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002451:Cell Compartmentation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004285:Dogs; D005455:Fluorescent Antibody Technique; D007365:Intercellular Junctions; D010446:Peptide Fragments / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D051178:alpha Catenin
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D051178:alpha Catenin