An Autoinhibited Structure of α-Catenin and Its Implications for Vinculin Recruitment to Adherens Junctions

• Published in: The Journal of biological chemistry 2013-05, Vol.288 (22), p.15913-15925
• Main Authors: Ishiyama, Noboru, Tanaka, Nobutoshi, Abe, Kentaro, Yang, Yoo Jeong, Abbas, Yazan M., Umitsu, Masataka, Nagar, Bhushan, Bueler, Stephanie A., Rubinstein, John L., Takeichi, Masatoshi, Ikura, Mitsuhiko
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - chemistry; Actin Cytoskeleton - genetics; Actin Cytoskeleton - metabolism; Adherens Junction; Adherens Junctions - chemistry; Adherens Junctions - genetics; Adherens Junctions - metabolism; alpha Catenin - chemistry; alpha Catenin - genetics; alpha Catenin - metabolism; Animals; Cadherins; Catenin; Cell Adhesion; Cell Biology; Cell Line; Crystallography, X-Ray; Cytoskeleton; Mice; Models, Biological; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Protein Structure, Tertiary; Structure-Activity Relationship; Vinculin; Vinculin - chemistry; Vinculin - genetics; Vinculin - metabolism; α-Catenin
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.453928

α-Catenin is an actin- and vinculin-binding protein that regulates cell-cell adhesion by interacting with cadherin adhesion receptors through β-catenin, but the mechanisms by which it anchors the cadherin-catenin complex to the actin cytoskeleton at adherens junctions remain unclear. Here we determined crystal structures of αE-catenin in the autoinhibited state and the actin-binding domain of αN-catenin. Together with the small-angle x-ray scattering analysis of full-length αN-catenin, we deduced an elongated multidomain assembly of monomeric α-catenin that structurally and functionally couples the vinculin- and actin-binding mechanisms. Cellular and biochemical studies of αE- and αN-catenins show that αE-catenin recruits vinculin to adherens junctions more effectively than αN-catenin, partly because of its higher affinity for actin filaments. We propose a molecular switch mechanism involving multistate conformational changes of α-catenin. This would be driven by actomyosin-generated tension to dynamically regulate the vinculin-assisted linkage between adherens junctions and the actin cytoskeleton. Background: α-Catenin is an actin-binding protein that recruits vinculin to adherens junctions. Results: An elongated autoinhibited structure of α-catenin indicates structural and functional coupling of its vinculin- and actin-binding mechanisms. Conclusion: The anchoring strength of adherens junctions is dynamically regulated by α-catenin to match the actomyosin-generated tension. Significance: Multistate conformations of α-catenin facilitate the direct and vinculin-assisted linkages between the cadherin-catenin complex and the actin cytoskeleton.