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J Biol Chem. 2016 Jul 22;291(30):15687-99. doi: 10.1074/jbc.M116.735423. Epub 2016 May 26.

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

Author information

1
From the Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261.
2
From the Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261 adamkwi@pitt.edu.

Abstract

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 whether 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 strongly 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, 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.

KEYWORDS:

actin; adherens junction; alpha-catenin (α-catenin); cadherin; cardiomyocyte

PMID:
27231342
PMCID:
PMC4957052
DOI:
10.1074/jbc.M116.735423
[Indexed for MEDLINE]
Free PMC Article

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