Assessment of the CTNNA3 gene encoding human αT-catenin regarding its involvement in dilated cardiomyopathy

Janssens, Barbara; Mohapatra, Bhagyalaxmi; Vatta, Matteo; Goossens, Steven; Vanpoucke, Griet; Kools, Patrick; Montoye, Tony; Hengel, Jolanda van; Bowles, Neil E.; Roy, Frans van; Towbin, Jeffrey A.

doi:10.1007/s00439-002-0857-5

Cited by 43 publications

(27 citation statements)

References 25 publications

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“…The observation that alpha3 and alpha2 share identical exon-exon boundaries [36] suggests to us that alpha3 evolved via a gene duplication of alpha2 coinciding with the origin of amniotes. Unlike alpha1 and alpha2, alpha3 interacts with pkp2 in the area composita (a hybrid adherens junction in the heart muscle), yet co-expresses with alpha1 at intercalated discs of cardiomyocytes [37].…”

Section: Discussionmentioning

confidence: 99%

The evolutionary history of the catenin gene family during metazoan evolution

2011

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BackgroundCatenin is a gene family composed of three subfamilies; p120, beta and alpha. Beta and p120 are homologous subfamilies based on sequence and structural comparisons, and are members of the armadillo repeat protein superfamily. Alpha does not appear to be homologous to either beta or p120 based on the lack of sequence and structural similarity, and the alpha subfamily belongs to the vinculin superfamily. Catenins link the transmembrane protein cadherin to the cytoskeleton and thus function in cell-cell adhesion. To date, only the beta subfamily has been evolutionarily analyzed and experimentally studied for its functions in signaling pathways, development and human diseases such as cancer. We present a detailed evolutionary study of the whole catenin family to provide a better understanding of how this family has evolved in metazoans, and by extension, the evolution of cell-cell adhesion.ResultsAll three catenin subfamilies have been detected in metazoans used in the present study by searching public databases and applying species-specific BLAST searches. Two monophyletic clades are formed between beta and p120 subfamilies using Bayesian phylogenetic inference. Phylogenetic analyses also reveal an array of duplication events throughout metazoan history. Furthermore, numerous annotation issues for the catenin family have been detected by our computational analyses.ConclusionsDelta2/ARVCF catenin in the p120 subfamily, beta catenin in the beta subfamily, and alpha2 catenin in the alpha subfamily are present in all metazoans analyzed. This implies that the last common ancestor of metazoans had these three catenin subfamilies. However, not all members within each subfamily were detected in all metazoan species. Each subfamily has undergone duplications at different levels (species-specific, subphylum-specific or phylum-specific) and to different extents (in the case of the number of homologs). Extensive annotation problems have been resolved in each of the three catenin subfamilies. This resolution provides a more coherent description of catenin evolution.

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Section: Discussionmentioning

confidence: 99%

The evolutionary history of the catenin gene family during metazoan evolution

2011

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“…Mammals possess three isoforms of α-catenin, termed αE-, αN-, and αT-catenin, which originated from the same ancestral gene and share the same location on human chromosome 10 (Janssens et al, 2003). αE-, αN-, and αT-catenin are expressed predominantly, but not exclusively, in epithelia, neurons, and heart/testis, respectively (Herrenknecht et al, 1991; Shapiro and Weis, 2009; Uchida et al, 1994).…”

Section: Functional Analysis Of CCC Evolutionmentioning

confidence: 99%

The Evolutionary Origin of Epithelial Cell–Cell Adhesion Mechanisms

Miller

Clarke

Weis

et al. 2013

Current Topics in Membranes

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SUMMARY A simple epithelium forms a barrier between the outside and the inside of an organism, and is the first organized multicellular tissue found in evolution. We examine the relationship between the evolution of epithelia and specialized cell-cell adhesion proteins comprising the classical cadherin/β-catenin/α-catenin complex (CCC). A review of the divergent functional properties of the CCC in metazoans and non-metazoans, and an updated phylogenetic coverage of the CCC using recent genomic data reveal: 1) The core CCC likely originated before the last common ancestor of unikonts and their closest bikont sister taxa. 2) Formation of the CCC may have constrained sequence evolution of the classical cadherin cytoplasmic domain and β-catenin in metazoa. 3) The α-catenin binding domain in β-catenin appears to be the favored mutation site for disrupting β-catenin function in the CCC. 4) The ancestral function of the α/β-catenin heterodimer appears to be an actin-binding module. In some metazoan groups, more complex functions of α-catenin were gained by sequence divergence in the non-actin binding (N-, M-) domains. 5) Allosteric regulation of α-catenin, rather than loss of function mutations, may have evolved for more complex regulation of the actin cytoskeleton.

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“…Genome-wide association (GWA) studies screening hundreds of thousands of single-nucleotide polymorphisms (SNPs) simultaneously using microarray systems have proved useful for identifying genetic changes that contribute to complex diseases. CTNNA3 is one of the largest genes in the human genome with 18 exons spanning 2.3 Mbp on chromosome 10q21 (Janssens et al, 2003). Two independent GWA studies identified multiple polymorphisms of CTNNA3 associated with increased susceptibility to toluene diisocyanate-induced asthma in Korean (Kim et al, 2009) and Canadian (Bernstein et al, 2013) workers.…”

Section: αT-catenin Function Outside the Heartmentioning

confidence: 99%

New functions for alpha-catenins in health and disease: from cancer to heart regeneration

Vite

Radice

2015

Cell Tissue Res

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Strong cell-cell adhesion mediated by adherens junctions is dependent on anchoring the transmembrane cadherin molecule to the underlying actin cytoskeleton. To do this, cadherin cytoplasmic domain interacts with catenin proteins, which include α-catenin that binds directly to filamentous actin. Originally thought to be a static structure, the connection between the cadherin/catenin adhesion complex and the actin cytoskeleton is now considered to be dynamic and responsive to both intercellular and intracellular signals. Alpha-catenins are mechanosensing proteins that undergo conformational change in response to cytoskeletal tension thus modifying the linkage between the cadherin and the actin cytoskeleton. There are three α-catenin isoforms expressed in mouse and human: αE-catenin (CTNNA1), αN-catenin (CTNNA2), and αT-catenin (CTNNA3). This review summarizes recent progress in understanding the in vivo function(s) of α-catenins in tissue morphogenesis, homeostasis, and disease. The role of α-catenin in the regulation of cellular proliferation will be discussed in the context of cancer and regeneration.

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Assessment of the CTNNA3 gene encoding human αT-catenin regarding its involvement in dilated cardiomyopathy

Cited by 43 publications

References 25 publications

The evolutionary history of the catenin gene family during metazoan evolution

The evolutionary history of the catenin gene family during metazoan evolution

The Evolutionary Origin of Epithelial Cell–Cell Adhesion Mechanisms

New functions for alpha-catenins in health and disease: from cancer to heart regeneration

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