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Using cAMP Sensors to Study Cardiac Nanodomains
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The Popeye Domain Containing Genes and Their Function as cAMP Effector Proteins in Striated Muscle

Cardiovascular Function, National Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Rm. 337, Du Cane Road, London W12 0NN, UK
J. Cardiovasc. Dev. Dis. 2018, 5(1), 18; https://doi.org/10.3390/jcdd5010018
Received: 27 February 2018 / Revised: 8 March 2018 / Accepted: 12 March 2018 / Published: 13 March 2018
(This article belongs to the Special Issue Cyclic Nucleotide Signaling and the Cardiovascular System)
The Popeye domain containing (POPDC) genes encode transmembrane proteins, which are abundantly expressed in striated muscle cells. Hallmarks of the POPDC proteins are the presence of three transmembrane domains and the Popeye domain, which makes up a large part of the cytoplasmic portion of the protein and functions as a cAMP-binding domain. Interestingly, despite the prediction of structural similarity between the Popeye domain and other cAMP binding domains, at the protein sequence level they strongly differ from each other suggesting an independent evolutionary origin of POPDC proteins. Loss-of-function experiments in zebrafish and mouse established an important role of POPDC proteins for cardiac conduction and heart rate adaptation after stress. Loss-of function mutations in patients have been associated with limb-girdle muscular dystrophy and AV-block. These data suggest an important role of these proteins in the maintenance of structure and function of striated muscle cells. View Full-Text
Keywords: Popeye domain; cAMP binding; effector protein; cardiac arrhythmia; limb-girdle muscular dystrophy; atrioventricular block Popeye domain; cAMP binding; effector protein; cardiac arrhythmia; limb-girdle muscular dystrophy; atrioventricular block
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Brand, T. The Popeye Domain Containing Genes and Their Function as cAMP Effector Proteins in Striated Muscle. J. Cardiovasc. Dev. Dis. 2018, 5, 18.

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