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Desmoglein-2 interaction is crucial for cardiomyocyte cohesion and function.
- Source :
-
Cardiovascular Research . Nov2014, Vol. 104 Issue 2, p245-257. 13p. - Publication Year :
- 2014
-
Abstract
- Aims We determined the contribution of the desmosomal cadherin desmoglein-2 to cell–cell cohesion in cardiomyocytes. In the intercalated disc, providing mechanical strength and electrical communication between adjacent cardiomyocytes, desmoglein-2 is closely associated with N-cadherin and gap junctions. Methods and results We studied intercalated discs of HL-1 cardiomyocytes by immunostaining of desmoglein-2 and N-cadherin. Cohesion was measured using a liberase-based dissociation-assay and compared with cell-free single-molecule atomic force microscopy measurements. l-tryptophan caused irregular desmoglein-2 condensation, weakened cell–cell cohesion and impaired both homophilic desmoglein-2 and N-cadherin trans-interaction, whereas l-phenylalanine had no effect. l-tryptophan did not affect N-cadherin localization and its inhibitory effect on cell-cohesion and desmoglein-2 binding, but not on N-cadherin interaction, was blocked by a desmoglein-specific tandem peptide. Moreover, Ca2+-depletion, desmoglein-2 knockdown, a desmoglein-specific single peptide and certain desmoglein-2 mutations associated with arrhythmogenic cardiomyopathy reduced cell–cell cohesion, whereas cell adhesion was strengthened by desmoglein-2 overexpression. Since single peptide did not interfere with N-cadherin trans-interaction, these data indicate that (i) desmoglein-2 binding is crucial for cardiomyocyte cohesion and (ii) l-tryptophan reduced both desmoglein-2 and N-cadherin binding, whereas single and tandem peptide can be used to specifically target desmoglein-2-mediated adhesion. l-tryptophan and single peptide also induced ultrastructural alterations of areae compositae. Functional analyses at the organ level revealed reduced cardiomyocyte function and inefficient response to adrenergic stimulation in both l-tryptophan- and single peptide-challenged murine Langendorff hearts paralleled by redistribution of connexin 43 in l-tryptophan-treated heart slices. Conclusion Our data demonstrate that desmoglein-2 plays a critical role in cardiomyocyte cohesion and function. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00086363
- Volume :
- 104
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Cardiovascular Research
- Publication Type :
- Academic Journal
- Accession number :
- 99301437
- Full Text :
- https://doi.org/10.1093/cvr/cvu206