The Popdc gene family in the rat: Molecular cloning, characterization and expression analysis in the heart and cultured cardiomyocytes

Parnes, Doris; Jacoby, Vered; Sharabi, Avital; Schlesinger, Hadassa; Brand, Thomas; Kessler‐Icekson, Gania

doi:10.1016/j.bbaexp.2007.06.001

Cited by 12 publications

(13 citation statements)

References 25 publications

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“…The post transcriptional regulation of POPDC1 during mouse post-natal development and the POPDC1 down-regulation by serum in cultured cardiomyocytes have been proposed, although no clear mechanism has been delineated (14,17). In the failing hearts we found the co-regulation of POPDC1 with POPDC3 but not with POPDC2, which correlated with MYHC7.…”

Section: Discussionsupporting

confidence: 52%

“…Total RNA was isolated (Trireagent, Sigma) and subjected to reverse transcription and quantitative polymerase chain reaction (RT-qPCR). Firststrand cDNA was synthesized in 20 μl reactions containing 1 μg total RNA, 100 U M-MLVRT (H-) reverse transcriptase (Promega, Madison, WI, USA) and 10 μM oligo(dT) [12][13][14][15][16][17][18] (17). Aliquots (0.02-1.5 μl) of each cDNA were taken for qPCR analysis (TaqMan technology, Applied Biosystems, Foster City, CA, USA) performed in the Prism 7700 Sequence Detection System.…”

Section: Methodsmentioning

confidence: 99%

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Popeye domain-containing 1 is down-regulated in failing human hearts

Gingold‐Belfer

Bergman²,

Alcalay³

et al. 2010

Int J Mol Med

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Abstract. Congestive heart failure, a complex disease of heterogeneous etiology, involves alterations in the expression of multiple genes. The Popeye domain-containing (POPDC) family of three novel muscle-restricted genes (POPDC1-3) is evolutionarily conserved and developmentally regulated. In mice, POPDC1 has been shown to play an important role in skeletal and cardiac muscles subjected to injury or stress. However, it has never been explored in human hearts. In biopsies from non-failing and failing human hearts, we examined the cellular distribution of POPDC1 as well as the expression patterns of POPDC1-3 mRNAs. POPDC1 was visualized by immunohistochemistry and estimated by Western immunoblotting. The mRNA levels of POPDC1-3 and ß myosin heavy chain (MYHC7) were assessed using reverse transcription/quantitative polymerase chain reaction. POPDC1 was predominantly localized in the sarcolemma with an enhanced expression in the intercalated discs. In failing hearts, many cardiomyocytes appeared deformed and POPDC1 labeling was deranged. The three POPDC mRNAs were expressed in the four heart chambers with higher transcript levels in the ventricles compared to the atria. Heart failure concurred with reduced levels of POPDC1 mRNA and protein in the left ventricle. Correlation analyses of mRNA levels among the failing heart specimens indicated the coordinated regulation of POPDC1 with POPDC3 and of POPDC2 with MYHC7. It can be concluded that POPDC gene expression is modified in end-stage heart failure in humans in a manner suggesting regulatory and/or functional differences between the three family members and that POPDC1 is particularly susceptible to this condition.

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Section: Discussionsupporting

confidence: 52%

Section: Methodsmentioning

confidence: 99%

Popeye domain-containing 1 is down-regulated in failing human hearts

Gingold‐Belfer

Bergman²,

Alcalay³

et al. 2010

Int J Mol Med

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“…It will also be important to study the phenotype of popdc1 and popdc3 morphants in zebrafish. It is likely that cardiac and skeletal muscle phenotypes are also present in these morphants given that in all vertebrates studied so far, the Popdc genes are expressed in muscle and heart (Andrée et al, 2000; Breher et al, 2004; Froese and Brand, 2008; Hitz et al, 2002; Parnes et al, 2007; Torlopp et al, 2006). …”

Section: Discussionmentioning

confidence: 99%

“…Popdc2 is uniquely present in vertebrates, whereas Popdc1 and Popdc3 orthologs are also found in lower chordates and insects (Brand, 2005; Lin et al, 2007). All three genes in vertebrates display an overlapping and evolutionary conserved expression pattern, being highly abundant in cardiac and skeletal muscle, suggesting an important function in these tissues (Andrée et al, 2000; Breher et al, 2004; Froese and Brand, 2008; Hitz et al, 2002; Parnes et al, 2007; Torlopp et al, 2006). Popdc genes are also expressed in other cell types such as smooth muscle cells, neurons, and several types of epithelial cells, which indicate a more wide-spread role for this gene family (Brand, 2005; Osler et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

The Popeye domain containing 2 (popdc2) gene in zebrafish is required for heart and skeletal muscle development

Kirchmaier

Poon

Schwerte

et al. 2012

Developmental Biology

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The Popeye domain containing (Popdc) genes encode a family of transmembrane proteins with an evolutionary conserved Popeye domain. These genes are abundantly expressed in striated muscle tissue, however their function is not well understood. In this study we have investigated the role of the popdc2 gene in zebrafish. Popdc2 transcripts were detected in the embryonic myocardium and transiently in the craniofacial and tail musculature. Morpholino oligonucleotide-mediated knockdown of popdc2 resulted in aberrant development of skeletal muscle and heart. Muscle segments in the trunk were irregularly shaped and craniofacial muscles were severely reduced or even missing. In the heart, pericardial edema was prevalent in the morphants and heart chambers were elongated and looping was abnormal. These pathologies in muscle and heart were alleviated after reducing the morpholino concentration. However the heart still was abnormal displaying cardiac arrhythmia at later stages of development. Optical recordings of cardiac contractility revealed irregular ventricular contractions with a 2:1, or 3:1 atrial/ventricular conduction ratio, which caused a significant reduction in heart frequency. Recordings of calcium transients with high spatiotemporal resolution using a transgenic calcium indicator line (Tg(cmlc2:gCaMP)s878) and SPIM microscopy confirmed the presence of a severe arrhythmia phenotype. Our results identify popdc2 as a gene important for striated muscle differentiation and cardiac morphogenesis. In addition it is required for the development of the cardiac conduction system.

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“…9; and also referred to as Bves; ref. 8), Popdc2 (previously known as Pop2), and Popdc3 (previously known as Pop3) (8,9,(12)(13)(14)(15). Popdc proteins contain 3 transmembrane helices and the evolutionary conserved cytoplasmic Popeye domain (10,11).…”

Section: Introductionmentioning

confidence: 99%

Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice

Froese

Breher²,

Waldeyer³

et al. 2012

J. Clin. Invest.

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137

455

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Cardiac pacemaker cells create rhythmic pulses that control heart rate; pacemaker dysfunction is a prevalent disorder in the elderly, but little is known about the underlying molecular causes. Popeye domain containing (Popdc) genes encode membrane proteins with high expression levels in cardiac myocytes and specifically in the cardiac pacemaking and conduction system. Here, we report the phenotypic analysis of mice deficient in Popdc1 or Popdc2. ECG analysis revealed severe sinus node dysfunction when freely roaming mutant animals were subjected to physical or mental stress. In both mutants, bradyarrhythmia developed in an age-dependent manner. Furthermore, we found that the conserved Popeye domain functioned as a high-affinity cAMP-binding site. Popdc proteins interacted with the potassium channel TREK-1, which led to increased cell surface expression and enhanced current density, both of which were negatively modulated by cAMP. These data indicate that Popdc proteins have an important regulatory function in heart rate dynamics that is mediated, at least in part, through cAMP binding. Mice with mutant Popdc1 and Popdc2 alleles are therefore useful models for the dissection of the mechanisms causing pacemaker dysfunction and could aid in the development of strategies for therapeutic intervention.

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The Popdc gene family in the rat: Molecular cloning, characterization and expression analysis in the heart and cultured cardiomyocytes

Cited by 12 publications

References 25 publications

Popeye domain-containing 1 is down-regulated in failing human hearts

Popeye domain-containing 1 is down-regulated in failing human hearts

The Popeye domain containing 2 (popdc2) gene in zebrafish is required for heart and skeletal muscle development

Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice

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