Alpha-catenin Is a Molecular Switch That Binds E-cadherin-beta-catenin and Regulates Actin-Filament Assembly

Cell. 2005 Dec 2;123(5):903-15. doi: 10.1016/j.cell.2005.09.021.

Abstract

Epithelial cell-cell junctions, organized by adhesion proteins and the underlying actin cytoskeleton, are considered to be stable structures maintaining the structural integrity of tissues. Contrary to the idea that alpha-catenin links the adhesion protein E-cadherin through beta-catenin to the actin cytoskeleton, in the accompanying paper we report that alpha-catenin does not bind simultaneously to both E-cadherin-beta-catenin and actin filaments. Here we demonstrate that alpha-catenin exists as a monomer or a homodimer with different binding properties. Monomeric alpha-catenin binds more strongly to E-cadherin-beta-catenin, whereas the dimer preferentially binds actin filaments. Different molecular conformations are associated with these different binding states, indicating that alpha-catenin is an allosteric protein. Significantly, alpha-catenin directly regulates actin-filament organization by suppressing Arp2/3-mediated actin polymerization, likely by competing with the Arp2/3 complex for binding to actin filaments. These results indicate a new role for alpha-catenin in local regulation of actin assembly and organization at sites of cadherin-mediated cell-cell adhesion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / chemistry
  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Adhesion / physiology*
  • Cell Membrane / metabolism
  • Cytoskeleton / metabolism
  • Dimerization
  • Mice
  • Models, Molecular
  • Multiprotein Complexes
  • Protein Binding
  • Protein Conformation*
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Vinculin / chemistry
  • Vinculin / genetics
  • Vinculin / metabolism
  • alpha Catenin / chemistry*
  • alpha Catenin / genetics
  • alpha Catenin / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • Cadherins
  • Multiprotein Complexes
  • Protein Subunits
  • Recombinant Proteins
  • alpha Catenin
  • beta Catenin
  • Vinculin