Direct interaction of the C-terminal domain of alpha-catenin and F-actin is necessary for stabilized cell-cell adhesion

Cell Commun Adhes. 2006 May-Jun;13(3):151-70. doi: 10.1080/15419060600726142.

Abstract

Alpha-catenin functions to anchor adherens junctions to the filamentous actin (F-actin) cytoskeleton, through direct and indirect binding mechanisms. When truncated at amino acid 865, alpha-catenin exhibited a markedly reduced F-actin binding affinity compared to wild-type. Expression of the truncated mutant in the alpha-catenin deficient colon carcinoma cell line, Clone A, could not restore an adhesive phenotype when compared. Furthermore, the truncated alpha-catenin fusion protein failed to concentrate at sites of cell-cell contact, to promote morphological changes associated with epithelial monolayers, and to stimulate resistance to shearing forces in a hanging drop aggregation assay. Subsequent attempts to isolate single residues governing the direct F-actin interaction, using neutralizing charge or reverse charge mutations of basic residues within a homology modeled alpha-catenin C-terminal 5-helix bundle, had no effect on F-actin cosedimentation. We conclude that direct attachment of alpha-catenin to F-actin is required to promote cadherin-mediated contact formation and strong cell-cell adhesive states.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism*
  • Cell Adhesion
  • Cell Aggregation
  • Cell Line, Tumor
  • DNA Mutational Analysis
  • Humans
  • Models, Molecular
  • Mutation / genetics
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / metabolism
  • Structural Homology, Protein
  • Tumor Cells, Cultured
  • alpha Catenin / chemistry*
  • alpha Catenin / genetics
  • alpha Catenin / metabolism*

Substances

  • Actins
  • Recombinant Fusion Proteins
  • alpha Catenin