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

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.

• Authors: Derek J Pappas, David L Rimm
• Journal: Cell communication & adhesion (Cell Commun Adhes) 2006 May-Jun Vol. 13 Issue 3 Pg. 151-70 ISSN: 1541-9061 [Print] England
• PMID: 16798615 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Actins
• Recombinant Fusion Proteins
• alpha Catenin

Topics

• 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, genetics, metabolism)