The area composita of adhering junctions connecting heart muscle cells of vertebrates. II. Colocalizations of desmosomal and fascia adhaerens molecules in the intercalated disk

Borrmann, Carola M.; Gründ, Christine; Kühn, Caecilia; Hofmann, Ilse; Pieperhoff, Sebastian; Franke, Werner W.

doi:10.1016/j.ejcb.2006.02.009

Cited by 127 publications

(110 citation statements)

References 132 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…Desmoglein and desmocollin, also members of the cadherin superfamily, are found in the desmosome where they interact with linker proteins such as plakoglobin and desmoplakin. Recent data indicate a hybrid junctional complex exists in the heart referred to as area composita where a combination of components from the adherens junction and desmosome colocalize and interact (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

N-cadherin haploinsufficiency affects cardiac gap junctions and arrhythmic susceptibility

Levin

Xiong

et al. 2008

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

Cardiac-specific deletion of the murine gene (Cdh2) encoding the cell adhesion molecule, Ncadherin, results in disassembly of the intercalated disc (ICD) structure and sudden arrhythmic death. Connexin 43 (Cx43)-containing gap junctions are significantly reduced in the heart after depleting N-cadherin, therefore we hypothesized that animals expressing half the normal levels of N-cadherin would exhibit an intermediate phenotype. We examined the effect of N-cadherin haploinsufficiency on Cx43 expression and susceptibility to induced arrhythmias in mice either wild-type or heterozygous for the Cx43 (Gja1)-null allele. An increase in hypophosphorylated Cx43 accompanied by a modest decrease in total Cx43 protein levels was observed in the N-cadherin heterozygous mice. Consistent with these findings N-cadherin heterozygotes exhibited increased susceptibility to ventricular arrhythmias compared to wild-type mice. Quantitative immunofluorescence microscopy revealed a reduction in size of large Cx43-containing plaques in the N-cadherin heterozygous animals compared to wild-type. Gap junctions were further decreased in number and size in the N-cad/Cx43 compound heterozygous mice with increased arrhythmic susceptibility compared to the single mutants. The scaffold protein, ZO-1, was reduced at the ICD in N-cadherin heterozygous cardiomyocytes providing a possible explanation for the reduction in Cx43 plaque size. These data provide further support for the intimate relationship between N-cadherin and Cx43 in the heart, and suggest that germline mutations in the human N-cadherin (Cdh2) gene may predispose patients to increased risk of cardiac arrhythmias.

show abstract

Section: Introductionmentioning

confidence: 99%

N-cadherin haploinsufficiency affects cardiac gap junctions and arrhythmic susceptibility

Levin

Xiong

et al. 2008

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

show abstract

“…For example, g-catenin/plakoglobin, p120, plakophilins and p0071 reside at both adherens and desmosomal junctions (Borrmann et al, 2006;Calkins et al, 2003;Hatzfeld et al, 2003;Johnson and Boekelheide, 2002;Kanno et al, 2008). Whereas b-catenin does not appear to bind desmosomal cadherins in vivo (Choi et al, 2009), it does associate and functionally interact with other (non-cadherin) transmembrane proteins, such as the epidermal growth factor receptor and MUC1 (Hoschuetzky et al, 1994;Yamamoto et al, 1997).…”

Section: Basics Of Catenin Structure and Functionmentioning

confidence: 99%

The catenin family at a glance

McCrea

2010

Journal of Cell Science

View full text Add to dashboard Cite

“…While most components identified, including a-and b-catenin, together with further armadillo proteins such as plakoglobin and proteins p120, p0071 and ARVCF, have also been found in other nonepithelial cells, 11,[35][36][37] it has been a surprise to find that the adherens junction plaques of all 32 myxomata examined contain an additional major armadillo protein, Pkp2, which so far has been considered to be a protein exclusive to desmosomes and to the composite junctions of cardiomyocytes. 12,17,35,43,44 As shown by Goossens et al, 45 the cardiomyocyte-specific plaque integration of Pkp2 is based on its binding to myocardial a-T-catenin, 45 a protein, however, that does not seem to be present in cardiac myxoma cells. Obviously, the specific molecular binding partners of Pkp2 and the mechanisms and functions of its acquisition to myxoma adherens junctions will have to be determined in future experiments.…”

Section: Discussionmentioning

confidence: 99%

“…The stable integration of Pkp2 in the adherens junctions of cardiac myxomata is functionally remarkable, as this protein is known as the only member of the plakophilin subfamily that occurs in all proliferatively active epithelial cells and is also an essential architectonic and cytoskeletal filamentanchoring molecule in the desmosomes and composite junctions of myocardial cells. In the latter it is necessary for heart formation and for the onset and coordination of rhythmic heart beat, 18,[44][45][46][47][48] be it directly or indirectly (for further involvements of sodium channels or gap junctions, see also recent knockdown experiments). [49][50][51][52] Most impressive in the discussions about possible functional roles of Pkp2 are certainly the recent reports that cardiac Pkp2 is by far the most sensitive protein, which in mutated forms can contribute to arrhythmogenic ventricular cardiomyopathies (ARVCs).…”

Section: Discussionmentioning

confidence: 99%

A novel kind of tumor type-characteristic junction: plakophilin-2 as a major protein of adherens junctions in cardiac myxomata

et al. 2010

View full text Add to dashboard Cite

Using novel antibodies of high avidity to-and specificity for-the constitutive desmosomal plaque protein, plakophilin-2 (Pkp2), in a systematic study of the molecular composition of junctions connecting the cells of soft tissue tumors, we have discovered with immunocytochemical, biochemical and electron microscopical methods, a novel type of adherens junctions in all 32 cardiac myxomata examined. These junctions contain cadherin-11 as their major transmembrane glycoprotein, which we could repeatedly show in colocalization with N-cadherin, anchored in a cytoplasmic plaque formed by a-and b-catenin, together with the further armadillo-type proteins plakoglobin, p120, p0071 and ARVCF. Surprisingly, all adherens junctions of these tumors contained, in addition, another major armadillo protein Pkp2, hitherto known as an obligatory and characteristic constituent of desmosomes in epithelium-derived tumors. We have not detected Pkp2 in a series of noncardiac myxomata studied in parallel. Therefore, we conclude that this acquisition of Pkp2, which we have recently also observed in some mesenchymally derived cells growing in culture, can also occur in tumorigenic transformations in situ. We propose to examine the marker value of Pkp2 in clinical diagnoses of cardiac myxomata and to develop Pkp2-targeted therapeutic reagents.

show abstract

The area composita of adhering junctions connecting heart muscle cells of vertebrates. II. Colocalizations of desmosomal and fascia adhaerens molecules in the intercalated disk

Cited by 127 publications

References 132 publications

N-cadherin haploinsufficiency affects cardiac gap junctions and arrhythmic susceptibility

N-cadherin haploinsufficiency affects cardiac gap junctions and arrhythmic susceptibility

The catenin family at a glance

A novel kind of tumor type-characteristic junction: plakophilin-2 as a major protein of adherens junctions in cardiac myxomata

Contact Info

Product

Resources

About