POPDC proteins and cardiac function

Brand, Thomas

doi:10.1042/bst20190249

Cited by 19 publications

(31 citation statements)

References 64 publications

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“…Turnover of intracellular cAMP is ensured by phosphodiesterases (PDEs), which hydrolyze cAMP into inactive 5 AMP ( Figure 1). There are four known cAMP effectors expressed in mammalian cells: the cAMP-dependent protein kinase (PKA) [25,26], the guanine nucleotide exchange factor Epac [27], the Popeye domain containing (Popdc) proteins [28], and the hyperpolarization cyclic nucleotide-gated (HCN) channels [29]. Among these effectors, only PKA and Epac exchange factors have been studied in cardiac fibroblasts.…”

Section: The Functional Role Of Camp Signaling In Cardiac Fibroblastsmentioning

confidence: 99%

The Role of Cyclic AMP Signaling in Cardiac Fibrosis

Delaunay

Osman

Kaiser

et al. 2019

Cells

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Myocardial stress and injury invariably promote remodeling of the cardiac tissue, which is associated with cardiomyocyte death and development of fibrosis. The fibrotic process is initially triggered by the differentiation of resident cardiac fibroblasts into myofibroblasts. These activated fibroblasts display increased proliferative capacity and secrete large amounts of extracellular matrix. Uncontrolled myofibroblast activation can thus promote heart stiffness, cardiac dysfunction, arrhythmias, and progression to heart failure. Despite the well-established role of myofibroblasts in mediating cardiac disease, our current knowledge on how signaling pathways promoting fibrosis are regulated and coordinated in this cell type is largely incomplete. In this respect, cyclic adenosine monophosphate (cAMP) signaling acts as a major modulator of fibrotic responses activated in fibroblasts of injured or stressed hearts. In particular, accumulating evidence now suggests that upstream cAMP modulators including G protein-coupled receptors, adenylyl cyclases (ACs), and phosphodiesterases (PDEs); downstream cAMP effectors such as protein kinase A (PKA) and the guanine nucleotide exchange factor Epac; and cAMP signaling organizers such as A-kinase anchoring proteins (AKAPs) modulate a variety of fundamental cellular processes involved in myocardial fibrosis including myofibroblast differentiation, proliferation, collagen secretion, and invasiveness. The current review will discuss recent advances highlighting the role of cAMP and AKAP-mediated signaling in regulating pathophysiological responses controlling cardiac fibrosis.

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Section: The Functional Role Of Camp Signaling In Cardiac Fibroblastsmentioning

confidence: 99%

The Role of Cyclic AMP Signaling in Cardiac Fibrosis

Delaunay

Osman

Kaiser

et al. 2019

Cells

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“…POPDC proteins consist of a short extracellular Nterminal sequence which is glycosylated, three transmembrane domains, a conserved intracellular Popeye domain and a variable C-terminal domain which is isoform-specific, contains regions of low complexity and may be phosphorylated [4]. POPDC1 exists at the plasma membrane as a homodimer, which is stabilised by disulphide bonds [5,6].…”

Section: Introductionmentioning

confidence: 99%

An interaction of heart disease-associated proteins POPDC1/2 with XIRP1 in transverse tubules and intercalated discs

Holt

Fuller

Schindler

et al. 2020

BMC Mol and Cell Biol

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Background Popeye domain-containing proteins 1 and 2 (POPDC1 and POPDC2) are transmembrane proteins involved in cyclic AMP-mediated signalling processes and are required for normal cardiac pacemaking and conduction. In order to identify novel protein interaction partners, POPDC1 and 2 proteins were attached to beads and compared by proteomic analysis with control beads in the pull-down of proteins from cultured human skeletal myotubes. Results There were highly-significant interactions of both POPDC1 and POPDC2 with XIRP1 (Xin actin binding repeat-containing protein 1), actin and, to a lesser degree, annexin A5. In adult human skeletal muscle, both XIRP1 and POPDC1/2 were present at the sarcolemma and in T-tubules. The interaction of POPDC1 with XIRP1 was confirmed in adult rat heart extracts. Using new monoclonal antibodies specific for POPDC1 and POPDC2, both proteins, together with XIRP1, were found mainly at intercalated discs but also at T-tubules in adult rat and human heart. Conclusions Mutations in human POPDC1, POPDC2 and in human XIRP1, all cause pathological cardiac arrhythmias, suggesting a possible role for POPDC1/2 and XIRP1 interaction in normal cardiac conduction.

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“…Recently, the cAMP interacting Popeye-domain-containing proteins (POPDC) have been identified to play a critical regulatory role in cardiac pace maker cells at both the sinoatrial and atrioventricular nodes modulating cardiac conduction [ 49 ]. POPDC proteins are located in several membrane compartments interacting with TREK 1 channels, caveolin 3, dysferlin and dystrophin to maintain the cardiomyocyte structure and function [ 50 , 51 ].…”

Section: Cyclic Nucleotide Signalling and Compartmentalizationmentioning

confidence: 99%

Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases

Sadek

Cachorro

El‐Armouche

et al. 2020

IJMS

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Phosphodiesterases (PDEs) are the principal superfamily of enzymes responsible for degrading the secondary messengers 3′,5′-cyclic nucleotides cAMP and cGMP. Their refined subcellular localization and substrate specificity contribute to finely regulate cAMP/cGMP gradients in various cellular microdomains. Redistribution of multiple signal compartmentalization components is often perceived under pathological conditions. Thereby PDEs have long been pursued as therapeutic targets in diverse disease conditions including neurological, metabolic, cancer and autoimmune disorders in addition to numerous cardiovascular diseases (CVDs). PDE2 is a unique member of the broad family of PDEs. In addition to its capability to hydrolyze both cAMP and cGMP, PDE2 is the sole isoform that may be allosterically activated by cGMP increasing its cAMP hydrolyzing activity. Within the cardiovascular system, PDE2 serves as an integral regulator for the crosstalk between cAMP/cGMP pathways and thereby may couple chronically adverse augmented cAMP signaling with cardioprotective cGMP signaling. This review provides a comprehensive overview of PDE2 regulatory functions in multiple cellular components within the cardiovascular system and also within various subcellular microdomains. Implications for PDE2- mediated crosstalk mechanisms in diverse cardiovascular pathologies are discussed highlighting the prospective use of PDE2 as a potential therapeutic target in cardiovascular disorders.

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POPDC proteins and cardiac function

Cited by 19 publications

References 64 publications

The Role of Cyclic AMP Signaling in Cardiac Fibrosis

The Role of Cyclic AMP Signaling in Cardiac Fibrosis

An interaction of heart disease-associated proteins POPDC1/2 with XIRP1 in transverse tubules and intercalated discs

Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases

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