ArticleJournal of the American College of Cardiology2015
Alterations in the interactome of serine/threonine protein phosphatase type-1 in atrial fibrillation patients.
Article in Journal of the American College of Cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- Evidence for a role of adverse sarcomere signaling in atrial fibrillation induction.Journal of molecular and cellular cardiology plus · 2026Review
- Cyclic AMP-dependent regulation of ryanodine receptors in healthy and diseased hearts.Journal of molecular and cellular cardiology · 2026Review
- Transcriptomics, Proteomics and Bioinformatics in Atrial Fibrillation: A Descriptive Review.Bioengineering (Basel, Switzerland) · 2025Review
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- PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation.Circulation research · 2023Article
- Enhanced CaCirculation research · 2023Article
- A modern automated patch-clamp approach for high throughput electrophysiology recordings in native cardiomyocytes.Communications biology · 2022Article
- DUSP5 promotes osteogenic differentiation through SCP1/2-dependent phosphorylation of SMAD1.Stem cells (Dayton, Ohio) · 2021Article
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- Article
- Mechanisms underlying pathological CaPflugers Archiv : European journal of physiology · 2021Review
- Loss of SPEG Inhibitory Phosphorylation of Ryanodine Receptor Type-2 Promotes Atrial Fibrillation.Circulation · 2020Article
- Molecular Basis of Atrial Fibrillation Pathophysiology and Therapy: A Translational Perspective.Circulation research · 2020Review
- Pro-Arrhythmic Signaling of Thyroid Hormones and Its Relevance in Subclinical Hyperthyroidism.International journal of molecular sciences · 2020Review
- Atrial Cardiomyopathy: An Unexplored Limb of Virchow's Triad for AF Stroke Prophylaxis.Frontiers in cardiovascular medicine · 2020Review
- Loss of Protein Phosphatase 1 Regulatory Subunit PPP1R3A Promotes Atrial Fibrillation.Circulation · 2019Article
- Protein Phosphatase 2A Regulates Cardiac NaCirculation research · 2019Article
- Rearrangement of the Protein Phosphatase 1 Interactome During Heart Failure Progression.Circulation · 2018Article
- Dissecting Clinical and Metabolomics Associations of Left Atrial Phasic Function by Cardiac Magnetic Resonance Feature Tracking.Scientific reports · 2018Article
- Calcium-mediated cellular triggered activity in atrial fibrillation.The Journal of physiology · 2017Review
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundAtrial fibrillation (AF) is the most common sustained cardiac arrhythmia, yet current pharmacological treatments are limited. Serine/threonine protein phosphatase type-1 (PP1), a major phosphatase in the heart, consists of a catalytic subunit (PP1c) and a large set of regulatory (R)-subunits that confer localization and substrate specificity to the holoenzyme. Previous studies suggest that PP1 is dysregulated in AF, but the mechanisms are unknown.
objectivesThe purpose of this study was to test the hypothesis that PP1 is dysregulated in paroxysmal atrial fibrillation (PAF) at the level of its R-subunits.
methodsCardiac lysates were coimmunoprecipitated with anti-PP1c antibody followed by mass spectrometry-based, quantitative profiling of associated R-subunits. Subsequently, label-free quantification (LFQ) was used to evaluate altered R-subunit-PP1c interactions in PAF patients. R-subunits with altered binding to PP1c in PAF were further studied using bioinformatics, Western blotting (WB), immunocytochemistry, and coimmunoprecipitation.
resultsA total of 135 and 78 putative PP1c interactors were captured from mouse and human cardiac lysates, respectively, including many previously unreported interactors with conserved PP1c docking motifs. Increases in binding were found between PP1c and PPP1R7, cold-shock domain protein A (CSDA), and phosphodiesterase type-5A (PDE5A) in PAF patients, with CSDA and PDE5A being novel interactors validated by bioinformatics, immunocytochemistry, and coimmunoprecipitation. WB confirmed that these increases in binding cannot be ascribed to their changes in global protein expression alone.
conclusionsSubcellular heterogeneity in PP1 activity and downstream protein phosphorylation in AF may be attributed to alterations in PP1c-R-subunit interactions, which impair PP1 targeting to proteins involved in electrical and Ca(2+) remodeling. This represents a novel concept in AF pathogenesis and may provide more specific drug targets for treating AF.
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