Effect of increased β-adrenergic stimulation on intercalated disc proteins in rat cardiomyocytes
- Abstract number
- European Microscopy Congress 2020
- Corresponding Email
- [email protected]
- LSA.2 - Dynamic interactions in cells, organoids, tissue and entire organisms
- Mr Mihai Pruna (1), Dr Elisabeth Ehler (1), Dr Mark Holt (1)
1. King's College London
intercalated disc desmosomes formins
- Abstract text
The intercalated disc, consisting of gap junctions, adherens junctions and desmosomes, is a highly organised structure in the heart, ensuring electrical and mechanical coupling between neighbouring cardiomyocytes. Its structure and composition are altered in cardiomyopathies such as dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (AC). A major change observed in the hearts of mouse models and patients with DCM is increased expression of adherens junction components (N-cadherin, β-catenin, plakoglobin, α-catenin) and filamentous actin (F-actin). It is currently unclear which protein is responsible for increased actin anchorage at the intercalated disc but one possible candidate is the formin FHOD1, localised at the intercalated disc with elevated levels in DCM. Nevertheless, whether FHOD1 plays any role in heart function remains controversial. The aim of this work is to investigate the expression and dynamics of several cell-cell contact proteins in neonatal rat cardiomyocytes (NRCs) in the presence and absence of increased β-adrenergic stimulation at several time points (1 hour, 6 hours, 1 day, 4 days) by immunofluorescence and confocal microscopy. Our results show that desmoglein2, a classical desmosomal protein is not present at the junctions in the early stages, whereas another desmosomal protein, plakophilin2, is already there. We observed that treatment with isoproterenol, a β-adrenergic agonist, increases the formation of plakoglobin spikes and increase phosphorylation of FHOD1 at the junctions (1 day). The levels of the desmosomal proteins plakophilin2 also appear to be increased after long term stimulation (4 days).
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