The Popeye Domain Containing Genes and cAMP Signaling.
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Published version
Author(s)
Brand, T
Poon, KL
Simrick, S
Schindler, RF
Type
Journal Article
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, 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.
Date Issued
2014-05-21
Date Acceptance
2014-05-07
Citation
Journal of Cardiovascular Development and Disease, 2014, 1 (1), pp.121-133
ISSN
2308-3425
Publisher
MDPI
Start Page
121
End Page
133
Journal / Book Title
Journal of Cardiovascular Development and Disease
Volume
1
Issue
1
Copyright Statement
© 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/3.0/).
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/3.0/).
Subjects
Popeye domain containing genes
cAMP
cAMP-binding proteins
cardiac arrhythmia
cardiac conduction system
fight-or-flight response
pacemaking
phosphate binding cassette
sinus node
Publication Status
Published