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Adrenergic signaling in the heart

Team: Andrea Ahles, Laura Hinz, Sabine Brummer, Karin Ziegler

Adrenoceptors are central mediators in the sympathetic nervous system, adjusting organ functions to maintain whole-body homeostasis under resting conditions. These G protein-coupled receptors group into three families, namely, the α1-, α2-, and β-adrenoceptors, with three family members each. Upon catecholamine binding, adrenoceptors change conformation, couple to and activate G proteins, and thereby initiate various intracellular signaling cascades. As the primary receivers and transducers of sympathetic activation, adrenoceptors have a central role in human physiology and disease and are important targets for widely used drugs such as β-blockers.
Our team focuses on optical recording of receptor conformation and second messenger formation in living cells in real-time (Rochais et al., J Clin Invest. 2007, Ahles et al., Sci Signal 2011, Ahles et al., J Biol Chem 2015). This approach allowed us to discover that genetic variation in β-adrenoceptors (SNPs) determines their signaling properties (Ahles & Engelhardt, Pharmacol Rev 2014). Current efforts concentrate on the elucidation of sympathetic regulation of individual cardiac cell types as well as on posttranslational modification of the receptor protein.