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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Actins / genetics
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Actins / metabolism
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Amino Acid Sequence
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Animals
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Binding Sites / genetics
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Cadherins / chemistry
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Cadherins / genetics
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Cadherins / metabolism*
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Caenorhabditis elegans / embryology
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Electrophoresis, Polyacrylamide Gel
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Embryo, Nonmammalian / embryology
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Embryo, Nonmammalian / metabolism
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Molecular Sequence Data
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Mutation
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Protein Binding
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Protein Multimerization
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Scattering, Small Angle
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Sequence Homology, Amino Acid
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Two-Hybrid System Techniques
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X-Ray Diffraction
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alpha Catenin / chemistry
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alpha Catenin / genetics
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alpha Catenin / metabolism*
Substances
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Actins
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Cadherins
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Caenorhabditis elegans Proteins
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Cytoskeletal Proteins
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HMP-2 protein, C elegans
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alpha Catenin
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Green Fluorescent Proteins