Antisense expression of a desmocollin gene in MDCK cells alters desmosome plaque assembly but does not affect desmoglein expression

Roberts, Gareth A.; Burdett, I. D. J.; Pidsley, Sara C.; King, Ian A.; Magee, Anthony I.; Buxton, Roger S.

doi:10.1016/s0171-9335(98)80034-4

Cited by 19 publications

(14 citation statements)

References 57 publications

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“…27 In vitro antisense experiments against DSC2, 28 expression of truncated DSG3 and DSG1 proteins, 29,30 and knockout mice of the DSG3 gene 31 all resulted in a decreased number of desmosomes, associated with increased asymmetry and detachment. These electron microscopy observations are in agreement with those obtained in 3 DSG2 mutations carriers herein reported, which show a decreased number of desmosomes as well as a widening of intercalated disc gap.…”

Section: Effect Of the Dsg2 Mutations At The Cellular Levelmentioning

confidence: 99%

Mutations in Desmoglein-2 Gene Are Associated With Arrhythmogenic Right Ventricular Cardiomyopathy

et al. 2006

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Background-Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive myocardial atrophy with fibrofatty replacement. The recent identification of causative mutations in plakoglobin, desmoplakin (DSP), and plakophilin-2 (PKP2) genes led to the hypothesis that ARVC is due to desmosomal defects. Therefore, desmoglein-2 (DSG2), the only desmoglein isoform expressed in cardiac myocytes, was screened in subjects with ARVC. Methods and Results-In a series of 80 unrelated ARVC probands, 26 carried a mutation in DSP (16%), PKP2 (14%), and transforming growth factor-␤3 (2.5%) genes; the remaining 54 were screened for DSG2 mutations by denaturing high-performance liquid chromatography and direct sequencing. Nine heterozygous DSG2 mutations (5 missense, 2 insertion-deletions, 1 nonsense, and 1 splice site mutation) were detected in 8 probands (10%). All probands fulfilled task force criteria for ARVC. An endomyocardial biopsy was obtained in 5, showing extensive loss of myocytes with fibrofatty tissue replacement. In 3 patients, electron microscopy investigation was performed, showing intercalated disc paleness, decreased desmosome number, and intercellular gap widening. Conclusions-This is the first investigation demonstrating DSG2 gene mutations in a significant number of ARVCunrelated probands. Cardiac phenotype is characterized clinically by typical ARVC features with frequent left ventricular involvement and morphologically by fibrofatty myocardial replacement and desmosomal remodeling. The presence of mutations in desmosomal encoding genes in 40% of cases confirms that many forms of ARVC are due to alterations in the desmosome complex.

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Section: Effect Of the Dsg2 Mutations At The Cellular Levelmentioning

confidence: 99%

Mutations in Desmoglein-2 Gene Are Associated With Arrhythmogenic Right Ventricular Cardiomyopathy

et al. 2006

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“…Using an antisense expression vector for Dsc 2, Dsc protein could be largely depleted from transfected cells, markedly reducing desmosome numbers between cultured cells [215]. As already established, these cells also elaborate adherence junctions with classical cadherins, and these were not affected by downregulation of Dsc 2 nor was the integrity of the cultured monolayer of cells.…”

Section: Cell-cell Adhesion Moleculesmentioning

confidence: 99%

Cell Adhesion Molecules in the Kidney: From Embryo to Adult

Perantoni¹

1999

Nephron Exp Nephrol

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Multiple members from every major family of cell adhesion molecules (CAMs) have been implicated in the development, maintenance, or repair of renal tissues and include several isoforms of integrins, cell-bound glycoproteins, cadherins, immunoglobulin cell adhesion molecules, and selectins. In combination, they mediate a variety of cell-basement membrane and cell-cell interactions believed to direct morphogenesis and cell migration and regulate cell growth and apoptosis, in addition to generating a functional barrier for blood filtration and helping manage inflammatory responses in the kidney. The expression of some CAMs is transient during and critical to normal nephrogenesis, varying with specific stages of development, but often ultimately resulting in the constitutive production of other members in mature tissues. While gene-targeting studies have successfully implicated individual CAMs in renal cell functions, e.g., α₃β₁ and α₈β₁ integrins, the loss of others bears no renal phenotype due to redundancy of homologous family members or to the severity of the defect early in embryogenesis. This review summarizes the studies of various CAMs found in normal embryonic or adult kidney, describes their spatiotemporal expression patterns, and discusses their involvement in renal processes.

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“…Both Dsg and Dsc are thought to be involved in extracellular trans interactions between adjacent cells (Chitaev and Troyanovsky, 1997;Dusek et al, 2007;Getsios et al, 2004;Marcozzi et al, 1998;Roberts et al, 1998;Runswick et al, 2001). How Dsc and Dsg combine to form adhesive bonds is unclear because different binding properties have been assigned to the most ubiquitously expressed isoforms (Dsg2 and Dsc2) depending on the assay used (Waschke, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…How Dsc and Dsg combine to form adhesive bonds is unclear because different binding properties have been assigned to the most ubiquitously expressed isoforms (Dsg2 and Dsc2) depending on the assay used (Waschke, 2008). Knockdown of Dsc2 (Roberts et al, 1998) or knockout of Dsg2 expression (Eshkind et al, 2002) results in a loss of functional desmosomes. In addition, Dsg2 and Dsc2 can be depleted from junctions by blocking their microtubule (MT)-mediated trafficking, each resulting in weakened adhesive strength (Nekrasova et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Different roles of cadherins in the assembly and structural integrity of the desmosome complex

Lowndes

Rakshit

Shafraz

et al. 2014

Journal of Cell Science

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Adhesion between cells is established by the formation of specialized intercellular junctional complexes, such as desmosomes. Desmosomes contain isoforms of two members of the cadherin superfamily of cell adhesion proteins, desmocollins (Dsc) and desmogleins (Dsg), but their combinatorial roles in desmosome assembly are not understood. To uncouple desmosome assembly from other cell-cell adhesion complexes, we used micro-patterned substrates of Dsc2aFc and/or Dsg2Fc and collagen IV; we show that Dsc2aFc, but not Dsg2Fc, was necessary and sufficient to recruit desmosome-specific desmoplakin into desmosome puncta and produce strong adhesive binding. Single-molecule force spectroscopy showed that monomeric Dsc2a, but not Dsg2, formed Ca 2+ -dependent homophilic bonds, and that Dsg2 formed Ca 2+ -independent heterophilic bonds with Dsc2a. A W2A mutation in Dsc2a inhibited Ca 2+ -dependent homophilic binding, similar to classical cadherins, and Dsc2aW2A, but not Dsg2W2A, was excluded from desmosomes in MDCK cells. These results indicate that Dsc2a, but not Dsg2, is required for desmosome assembly through homophilic Ca 2+ -and W2-dependent binding, and that Dsg2 might be involved later in regulating a switch to Ca 2+ -independent adhesion in mature desmosomes.

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Antisense expression of a desmocollin gene in MDCK cells alters desmosome plaque assembly but does not affect desmoglein expression

Cited by 19 publications

References 57 publications

Mutations in Desmoglein-2 Gene Are Associated With Arrhythmogenic Right Ventricular Cardiomyopathy

Mutations in Desmoglein-2 Gene Are Associated With Arrhythmogenic Right Ventricular Cardiomyopathy

Cell Adhesion Molecules in the Kidney: From Embryo to Adult

Different roles of cadherins in the assembly and structural integrity of the desmosome complex

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