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The Popeye Domain Containing Genes and cAMP Signaling

Harefield Heart Science Centre, National Heart and Lung Institute (NHLI), Imperial College London, Hill End Road, Harefield UB96JH, UK
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Current affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
J. Cardiovasc. Dev. Dis. 2014, 1(1), 121-133; https://doi.org/10.3390/jcdd1010121
Received: 3 April 2014 / Revised: 6 May 2014 / Accepted: 7 May 2014 / Published: 21 May 2014
3'-5'-cyclic adenosine monophosphate (cAMP) is a second messenger, which plays an important role in the heart. It is generated in response to activation of G-protein-coupled receptors (GPCRs). Initially, it was thought that protein kinase A (PKA) exclusively mediates cAMP-induced cellular responses such as an increase in cardiac contractility, relaxation, and heart rate. With the identification of the exchange factor directly activated by cAMP (EPAC) and hyperpolarizing cyclic nucleotide-gated (HCN) channels as cAMP effector proteins it became clear that a protein network is involved in cAMP signaling. The Popeye domain containing (Popdc) genes encode yet another family of cAMP-binding proteins, which are prominently expressed in the heart. Loss-of-function mutations in mice are associated with cardiac arrhythmia and impaired skeletal muscle regeneration. Interestingly, the cardiac phenotype, which is present in both, Popdc1 and Popdc2 null mutants, is characterized by a stress-induced sinus bradycardia, suggesting that Popdc proteins participate in cAMP signaling in the sinuatrial node. The identification of the two-pore channel TREK-1 and Caveolin 3 as Popdc-interacting proteins represents a first step into understanding the mechanisms of heart rate modulation triggered by Popdc proteins. View Full-Text
Keywords: Popeye domain containing genes; cAMP; phosphate binding cassette; cAMP-binding proteins; pacemaking; cardiac arrhythmia; fight-or-flight response; sinus node; cardiac conduction system Popeye domain containing genes; cAMP; phosphate binding cassette; cAMP-binding proteins; pacemaking; cardiac arrhythmia; fight-or-flight response; sinus node; cardiac conduction system
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Brand, T.; Poon, K.L.; Simrick, S.; Schindler, R.F.R. The Popeye Domain Containing Genes and cAMP Signaling. J. Cardiovasc. Dev. Dis. 2014, 1, 121-133.

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