title: The Popeye Domain Containing Genes and cAMP Signaling.
abstract: 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,Popdc1andPopdc2null 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.
authors: Harefield Heart Science Centre, National Heart and Lung Institute (NHLI), Imperial College London, Hill End Road, Harefield UB96JH, UK.
authors: Thomas
authors: T
authors: Brand
authors: Harefield Heart Science Centre, National Heart and Lung Institute (NHLI), Imperial College London, Hill End Road, Harefield UB96JH, UK.
authors: Kar Lai
authors: KL
authors: Poon
authors: Harefield Heart Science Centre, National Heart and Lung Institute (NHLI), Imperial College London, Hill End Road, Harefield UB96JH, UK.
authors: Subreena
authors: S
authors: Simrick
authors: Harefield Heart Science Centre, National Heart and Lung Institute (NHLI), Imperial College London, Hill End Road, Harefield UB96JH, UK.
authors: Roland F R
authors: RF
authors: Schindler
keywords: Popeye domain containing genes; cAMP; cAMP-binding proteins; cardiac arrhythmia; cardiac conduction system; fight-or-flight response; pacemaking; phosphate binding cassette; sinus node