In vitro and in vivo reconstitution of the cadherin-catenin-actin complex from Caenorhabditis elegans.

Publication Type:

Journal Article

Source:

Proceedings of the National Academy of Sciences of the United States of America, Volume 107, Issue 33, p.14591-6 (2010)

Keywords:

Actinsdigestive disease, digestive deseases alpha Catenindigestive disease, digestive deseases Amino Acid Sequencedigestive disease, digestive deseases Animalsdigestive disease, digestive deseases Binding Sitesdigestive disease, digestive deseases Cadherinsdigestive disease, digestive deseases Caenorhabditis elegansdigestive disease, digestive deseases Caenorhabditis elegans Proteinsdigestive disease, digestive deseases Cytoskeletal Proteinsdigestive disease, digestive deseases Electrophoresis, Polyacrylamide Geldigestive disease, digestive deseases Embryo, Nonmammaliandigestive disease, digestive deseases Green Fluorescent Proteinsdigestive disease, digestive deseases Molecular Sequence Datadigestive disease, digestive deseases Mutationdigestive disease, digestive deseases Protein Bindingdigestive disease, digestive deseases Protein Multimerizationdigestive disease, digestive deseases Scattering, Small Angledigestive disease, digestive deseases Sequence Homology, Amino Aciddigestive disease, digestive deseases Two-Hybrid System Techniquesdigestive disease, digestive deseases X-Ray Diffraction

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.