ArticleThe Journal of clinical investigation2012
Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 156 citations in OpenAlex.
- Genetic susceptibility to cognitive decline following craniospinal irradiation for pediatric central nervous system tumors.Neuro-oncology · 2023Pooled it
- Mosapride promotes internalization of a TREK1-HTR4 complex and exerts rapid antidepressant-like effects.Molecular psychiatry · 2026Article
- TheBiology · 2025Article
- Bi-allelic variants in POPDC2 cause an autosomal recessive syndrome presenting with cardiac conduction defects and hypertrophic cardiomyopathy.American journal of human genetics · 2025Article
- Loss of popdc3 Impairs Mitochondrial Function and Causes Skeletal Muscle Atrophy and Reduced Swimming Ability in Zebrafish.Journal of cachexia, sarcopenia and muscle · 2025Article
- Human-specific epigenomic states in spermatogenesis.Computational and structural biotechnology journal · 2024Article
- Whole-genome sequencing reveals genetic structure and adaptive genes in Nepalese buffalo breeds.BMC genomics · 2024Article
- Activation of IPAmerican journal of physiology. Heart and circulatory physiology · 2024Article
- Cardiomyocyte-derived circulating extracellular vesicles allow a non-invasive liquid biopsy of myocardium in health and disease.medRxiv : the preprint server for health sciences · 2024Article
- Zebrafish Congenital Heart Disease Models: Opportunities and Challenges.International journal of molecular sciences · 2024Review
- Popeye domain containing proteins modulate the voltage-gated cardiac sodium channel Nav1.5.iScience · 2024Article
- Article
- Emerging Signaling Regulation of Sinoatrial Node Dysfunction.Current cardiology reports · 2023Review
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Genetics of sinoatrial node function and heart rate disorders.Disease models & mechanisms · 2023Review
- Defective BVES-mediated feedback control of cAMP in muscular dystrophy.Nature communications · 2023Article
- Systemic AAV9.BVES delivery ameliorates muscular dystrophy in a mouse model of LGMDR25.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Differential effects of mutations of POPDC proteins on heteromeric interaction and membrane trafficking.Acta neuropathologica communications · 2023Article
- TREK channels in Mechanotransduction: a Focus on the Cardiovascular System.Frontiers in cardiovascular medicine · 2023Review
- POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK-1 in heart.EMBO reports · 2022Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 7 institutions in 2 countries.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.