ArticleCirculation2019
Loss of Protein Phosphatase 1 Regulatory Subunit PPP1R3A Promotes Atrial Fibrillation.
Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 73 citations in OpenAlex.
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- Cyclic AMP-dependent regulation of ryanodine receptors in healthy and diseased hearts.Journal of molecular and cellular cardiology · 2026Review
- 2-Aminoethoxydiphenyl borate induces arrhythmias via Cx43-S282 dephosphorylation.In vitro cellular & developmental biology. Animal · 2026Article
- NOD1 is a key mediator of atrial myopathy in heart failure.Theranostics · 2026Article
- The interaction between sarcoplasmic reticulum and mitochondria: a novel mechanism for cardiac arrhythmia.Frontiers in physiology · 2026Review
- Acute Myeloid Leukemia Drives Atrial Fibrillation Through TNFα Signaling Activation.JACC. CardioOncology · 2025Article
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- Atlas of lysine propionylation of human right atrium and ALDH6A1-NADH pathway in new-onset atrial fibrillation after coronary surgery.Communications biology · 2025Article
- Electrophysiological Mechanisms and Therapeutic Potential of Calcium Channels in Atrial Fibrillation.Reviews in cardiovascular medicine · 2025Review
- ARID5A orchestrates cardiac aging and inflammation through MAVS mRNA stabilization.Nature cardiovascular research · 2025Article
- Sex-specific response to A1BG loss results in female dilated cardiomyopathy.Biology of sex differences · 2025Article
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- Rare Variant inCirculation. Genomic and precision medicine · 2024Article
- RyR2 Stabilizer Attenuates Cardiac Hypertrophy by Downregulating TNF-α/NF-κB/NLRP3 Signaling Pathway through Inhibiting Calcineurin.Journal of cardiovascular translational research · 2024Article
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
- Article
- Integrative human atrial modelling unravels interactive protein kinase A and Ca2+/calmodulin-dependent protein kinase II signalling as key determinants of atrial arrhythmogenesis.Cardiovascular research · 2023Article
- PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy.iScience · 2023Article
- PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation.Circulation research · 2023Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 4 countries.
Funding
Abstract
backgroundAbnormal calcium (Ca
methodsImmunoprecipitation, mass spectrometry, and complexome profiling were performed from the atrial tissue of patients with AF and from cardiac lysates of wild-type and Pln-knockout mice. Ppp1r3a-knockout mice were generated by CRISPR-mediated deletion of exons 2 to 3. Ppp1r3a-knockout mice and wild-type littermates were subjected to in vivo programmed electrical stimulation to determine AF susceptibility. Isolated atrial cardiomyocytes were used for Stimulated Emission Depletion superresolution microscopy and confocal Ca
resultsProteomics identified the PP1-regulatory subunit PPP1R3A as a novel RyR2-binding partner, and coimmunoprecipitation confirmed PPP1R3A binding to RyR2 and PLN. Complexome profiling and Stimulated Emission Depletion imaging revealed that PLN is present in the PPP1R3A-RyR2 interaction, suggesting the existence of a previously unknown SR nanodomain composed of both RyR2 and PLN/sarco/endoplasmic reticulum calcium ATPase-2a macromolecular complexes. This novel RyR2/PLN/sarco/endoplasmic reticulum calcium ATPase-2a complex was also identified in human atria. Genetic ablation of Ppp1r3a in mice impaired binding of PP1 to both RyR2 and PLN. Reduced PP1 targeting was associated with increased phosphorylation of RyR2 and PLN, aberrant SR-Ca
conclusionsPPP1R3A is a novel PP1-regulatory subunit within the RyR2 channel complex. Reduced PPP1R3A levels impair PP1 targeting and increase phosphorylation of both RyR2 and PLN. PPP1R3A deficiency promotes abnormal SR-Ca
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