αT-Catenin Is a Constitutive Actin-binding α-Catenin That Directly Couples the Cadherin·Catenin Complex to Actin Filaments

alpha-Catenin is the primary link between the cadherin center dot catenin complex and the actin cytoskeleton. Mammalian alpha E-catenin is allosterically regulated: the monomer binds the beta-catenin center dot cadherin complex, whereas the homodimer does not bind beta-catenin but interacts with F-actin. As part of the cadherin center dot catenin complex, alpha E-catenin requires force to bind F-actin strongly. It is not known whether these properties are conserved across the mammalian alpha-catenin family. Here we show that alpha T (testes)-catenin, a protein unique to amniotes that is expressed predominantly in the heart, is a constitutive actin-binding alpha-catenin. We demonstrate that alpha T-catenin is primarily a monomer in solution and that alpha T-catenin monomer binds F-actin in cosedimentation assays as strongly as alpha E-catenin homodimer. The beta-catenin center dot alpha T-catenin heterocomplex also binds F-actin with high affinity unlike the beta-catenin center dot alpha E-catenin complex, indicating that alpha T-catenin can directly link the cadherin center dot catenin complex to the actin cytoskeleton. Finally, we show that a mutation in alpha T-catenin linked to arrhythmogenic right ventricular cardiomyopathy, V94D, promotes homodimerization, blocks beta-catenin binding, and in cardiomyocytes disrupts localization at cell-cell contacts. Together, our data demonstrate that alpha T-catenin is a constitutively active actin-binding protein that can physically couple the cadherin center dot catenin complex to F-actin in the absence of tension. We speculate that these properties are optimized to meet the demands of cardiomyocyte adhesion.