Regulation of cardiomyocyte cohesion and arrhythmogenic cardiomyopathy
Sunil Yeruva and Jens Waschke (group leader)
Silvana Olivares-Baerwald (postdoctoral fellow)
Angela Wölfel (postdoctoral fellow)
Ellen Kempf (MD student)
Kilian Skowranek (technician)
The myocardium predominantly consists of cardiomyocytes which require strong coupling in order to maintain heart function. Adjacent cardiomyocytes are linked via complex connecting structures, the intercalated discs (ICD). These structures are composed of desmosomes, adherens junctions and gap junctions (Figure 1). Desmosomes, together with adherens junctions, provide cardiomyocyte cohesive strength necessary for strong mechanical coupling. They consist of the transmembrane adhesion molecules Dsg2 and desmocollin 2 (Dsc2), which are linked to the desmin intermediate filament system via the plaque proteins Pg, plakophilin 2 (Pkp2) and desmoplakin (DP) (Figure 1).
Mutations affecting the desmosomal components of the ICD can cause Arrythmogenic cardiomyopathy (AC), at least in part because they modulate the functions of the gap junctions composed of connexin 43. Therefore, we investigate the mechanisms by which cardiomyocyte cohesion is regulated and how desmosomal contacts control gap junctions (1). Especially, since we found that the adrenergic β1-receptor is localized at the ICD (Figure 2) we study how cAMP affects Dsg2-mediated adhesion. With this respect, we found that adrenergic signalling stabilizes cardiomyocyte cohesion, a new function of sympathetic signalling in the heart which we refer to as positive adhesiotropy (2).
Schinner C, Erber BM, Yeruva S, Waschke J (2018) Regulation of cardiac myocyte cohesion and gap junctions via desmosomal adhesion. Acta Physiol (Oxf). Dec 23:e13242. Epub ahead of print.
Schinner C, Vielmuth F, Rötzer, V, Hiermaier M, Radeva M, Co TK, Hartlieb E, Schmidt A, Imhof A, Messoudi A, Horn A, Schlipp A, Spindler V, Waschke J (2017) Adrenergic signaling strengthens cardiac myocyte cohesion, Circ Res.120(8):1305-1317
Schlipp A, Schinner C, Spindler V, Vielmuth F, Gehmlich K, Syrris P, McKenna WJ, Dendorfer A, Hartlieb E, Waschke J. (2014) Desmoglein-2 interaction is crucial for cardiomyocyte cohesion and function. Cardiovasc Res, 104(2):245-57