Abstract
The Popeye domain-containing (POPDC) gene family, consisting of Popdc1 (also known as Bves), Popdc2, and Popdc3, encodes transmembrane proteins abundantly expressed in striated muscle. POPDC proteins have recently been identified as cAMP effector proteins and have been proposed to be part of the protein network involved in cAMP signaling. However, their exact biochemical activity is presently poorly understood. Loss-of-function mutations in animal models causes abnormalities in skeletal muscle regeneration, conduction, and heart rate adaptation after stress. Likewise, patients carrying missense or nonsense mutations in POPDC genes have been associated with cardiac arrhythmias and limb-girdle muscular dystrophy. In this review, we introduce the POPDC protein family, and describe their structure function, and role in cAMP signaling. Furthermore, the pathological phenotypes observed in zebrafish and mouse models and the clinical and molecular pathologies in patients carrying POPDC mutations are described.
Highlights
The Role of Popeye domain-containing (POPDC) Proteins inThe heart consists of two different kinds of myocytes, i.e., the working or forceproducing cardiac myocytes found in the atrial and ventricular chambers, and the nodal and conducting myocytes forming the cardiac conduction system (CCS)
Loss of POPDC genes in model organisms are associated with cardiac arrhythmia and we review the current state of knowledge
protein kinase A (PKA) inhibition blocks enhanced long-term potentiation (LTP) formation in Popdc1 null mutants, which suggests that POPDC proteins similar to its function in cardiac myocytes are probably involved in fine tuning and limiting LTP formation by preventing PKA-driven phosphorylation of target proteins in response to subthreshold LTP-inducing stimuli [115]
Summary
The heart consists of two different kinds of myocytes, i.e., the working or forceproducing cardiac myocytes found in the atrial and ventricular chambers, and the nodal and conducting myocytes forming the cardiac conduction system (CCS). The CCS spontaneously generates and propagates electrical activity to trigger the synchronous and consecutive contraction of the atrial and ventricular chambers [1,2]. Synchronous electrical activation of the ventricular chambers is achieved by rapid propagation of the action potential from the base to the apex via the His bundle and bundle branches, which are running along the ventricular septum [2]. The distal part of the ventricular CCS is made up of the Purkinje fiber (PF) network Like the His bundle and bundle branches, PF have fast conduction properties, allowing an electrical activation of the ventricles from the apex to base, which is essential for efficient blood pumping of the ventricular chambers. Are novel mediators of cyclic nucleotide signaling and we briefly review this signaling pathway and discuss the role of POPDC proteins in this context. We give an outlook and identify areas where novel insight will be required in the future
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