α-Catenin is the primary link between the cadherin/catenin complex and the actin cytoskeleton. Mammalian αE-catenin is allosterically regulated: the monomer binds the β-catenin/cadherin complex, whereas the homodimer does not bind β-catenin but interacts with F-actin. As part of the cadherin/catenin complex, αE-catenin requires force to bind F-actin strongly. It is not known if these properties are conserved across the mammalian α-catenin family. Here we show that αT(Testes)-catenin, a protein unique to amniotes that is expressed predominantly in the heart, is a constitutive actin-binding α-catenin. We demonstrate that αT-catenin is primarily a monomer in solution and that αT-catenin monomer binds F-actin in cosedimentation assays as strong as αE-catenin homodimer. The β-catenin/αT-catenin heterocomplex also binds F-actin with high affinity, unlike the β-catenin/αE-catenin complex, indicating that αT-catenin can directly link the cadherin/catenin complex to the actin cytoskeleton. Finally, we show that a mutation in αT-catenin linked to arrhythmogenic right ventricular cardiomyopathy (ARVC) - V94D -promotes homodimerization, blocks β-catenin binding and, in cardiomyocytes, disrupts localization at cell-cell contacts. Together, our data demonstrate that αT-catenin is a constitutively active actin-binding protein that can physically couple the cadherin-catenin complex to F-actin in the absence of tension. We speculate that these properties are optimized to meet the demands of cardiomyocyte adhesion.
Wickline, E. D., Dale, I. W., Merkel, C. D., Heier, J. A., Stolz, D. B., & Kwiatkowski, A. V. (2016). αT-catenin is a constitutive actin-binding α-catenin that directly couples the cadherin·catenin complex to actin filaments. Journal of Biological Chemistry, 291(30), 15687–15699. https://doi.org/10.1074/jbc.M116.735423