Beschreibung:
<jats:p>Cardiomyocytes are electrically and mechanically coupled via intercalated discs (ICDs) composed of desmosomes, adherens junctions and gap junctions. The desmosomal cadherins desmoglein 2 (Dsg2) and desmocollin 2 and the classical cadherin N‐cadherin are the transmembrane adhesion molecules of the ICD and provide intercellular adhesive strength. Gap junctions dynamically remodel to adapt to cyclic adenosine 5′‐monophosphate (cAMP) signaling. It is unknown whether such rapid adaption also is evident for the adhesive function of the ICD. Atomic force microscopy revealed that cAMP signaling enhanced the number of Dsg2‐specific interactions along cell junctions and elevated their binding forces. This was accompanied by increased cell cohesion in cardiomyocyte cultures and murine heart slices. Enhanced Dsg2 staining along cell borders and increased junction length reflected cAMP‐induced reorganization of ICDs. cAMP signaling induced PKA‐dependent phosphorylation of the ICD plaque protein plakoglobin (Pg). In line with this, Pg deficiency abrogated cAMP‐mediated junctional remodeling and prevented increased cohesion in cardiac slices. Here we provide evidence that cAMP signaling strengthens cardiomyocyte cohesion in a Pg‐dependent manner. This mechanism may be of high medical relevance because reduced Pg levels at intercalated discs were shown to be a consistent feature of arrythmogenic cardiomyopathy.</jats:p>