An autoinhibited structure of ?-catenin and its implications for vinculin recruitment to adherens junctions.

ABSTRACT: ?-Catenin is an actin- and vinculin-binding protein that regulates cell-cell adhesion by interacting with cadherin adhesion receptors through ?-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 ?E-catenin in the autoinhibited state and the actin-binding domain of ?N-catenin. Together with the small-angle x-ray scattering analysis of full-length ?N-catenin, we deduced an elongated multidomain assembly of monomeric ?-catenin that structurally and functionally couples the vinculin- and actin-binding mechanisms. Cellular and biochemical studies of ?E- and ?N-catenins show that ?E-catenin recruits vinculin to adherens junctions more effectively than ?N-catenin, partly because of its higher affinity for actin filaments. We propose a molecular switch mechanism involving multistate conformational changes of ?-catenin. This would be driven by actomyosin-generated tension to dynamically regulate the vinculin-assisted linkage between adherens junctions and the actin cytoskeleton.

SUBMITTER: Ishiyama N 

PROVIDER: S-EPMC3668747 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature