title: In vitro and in vivo reconstitution of the cadherin-catenin-actin complex from Caenorhabditis elegans.
abstract: The ternary complex of cadherin, beta-catenin, and alpha-catenin regulates actin-dependent cell-cell adhesion. alpha-Catenin can bind beta-catenin and F-actin, but in mammals alpha-catenin either binds beta-catenin as a monomer or F-actin as a homodimer. It is not known if this conformational regulation of alpha-catenin is evolutionarily conserved. The Caenorhabditis elegans alpha-catenin homolog HMP-1 is essential for actin-dependent epidermal enclosure and embryo elongation. Here we show that HMP-1 is a monomer with a functional C-terminal F-actin binding domain. However, neither full-length HMP-1 nor a ternary complex of HMP-1-HMP-2(beta-catenin)-HMR-1(cadherin) bind F-actin in vitro, suggesting that HMP-1 is auto-inhibited. Truncation of either the F-actin or HMP-2 binding domain of HMP-1 disrupts C. elegans development, indicating that HMP-1 must be able to bind F-actin and HMP-2 to function in vivo. Our study defines evolutionarily conserved properties of alpha-catenin and suggests that multiple mechanisms regulate alpha-catenin binding to F-actin.
authors.affiliation: Department of Biology, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
authors.forename: Adam V
authors.initials: AV
authors.lastname: Kwiatkowski
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Maiden
authors.forename: Sabine
authors.initials: S
authors.lastname: Pokutta
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Choi
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Benjamin
authors.forename: Allison M
authors.initials: AM
authors.lastname: Lynch
authors.forename: W James
authors.initials: WJ
authors.lastname: Nelson
authors.forename: William I
authors.initials: WI
authors.lastname: Weis
authors.forename: Jeff
authors.initials: J
authors.lastname: Hardin
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D053838:Scattering, Small Angle; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D014961:X-Ray Diffraction; D051178:alpha Catenin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; C442473:HMP-2 protein, C elegans; D051178:alpha Catenin; D049452:Green Fluorescent Proteins