ArticleProceedings of the National Academy of Sciences of the United States of America2014
Myosin binding protein-C activates thin filaments and inhibits thick filaments in heart muscle cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 137 citations in OpenAlex.
- Evidence for a role of adverse sarcomere signaling in atrial fibrillation induction.Journal of molecular and cellular cardiology plus · 2026Review
- Fast skeletal myosin binding protein-C expression exacerbates dysfunction in heart failure.Basic research in cardiology · 2026Article
- Mavacamten shows broad benefit in human and mouse models of MYBPC3-related hypertrophic cardiomyopathy.Nature cardiovascular research · 2026Article
- Myosin Filaments of Vertebrate Skeletal and Cardiac Muscle are Highly Similar, but not Identical.bioRxiv : the preprint server for biology · 2026Article
- Spatial control of myosin regulatory light chain phosphorylation modulates cardiac thick filament mechanosensing.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cardiac myosin-binding protein-C acts as a tunable load sensor to regulate afterload dependence of ventricular function.American journal of physiology. Heart and circulatory physiology · 2025Article
- LncRNA Foxo6os as a Novel " Scaffold" Mediates MYBPC3 in Combating Pathological Cardiac Hypertrophy and Heart Failure.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Myocardium From Patients With ATTR Amyloidosis Produces Less Force Secondary to Increased Fibrosis.JACC. Basic to translational science · 2025Article
- Dual-filament regulation of relaxation in mammalian fast skeletal muscle.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Modeling the effects of thin filament near-neighbor cooperative interactions in mammalian myocardium.The Journal of general physiology · 2025Article
- cMyBP-C in hypertrophic cardiomyopathy: gene therapy and small-molecule innovations.Frontiers in cardiovascular medicine · 2025Review
- Functional control of myosin motors in the cardiac cycle.Nature reviews. Cardiology · 2025Review
- An integrated picture of the structural pathways controlling the heart performance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural changes in troponin during activation of skeletal and heart muscle determined in situ by polarised fluorescence.Biophysical reviews · 2024Review
- Load-dependence of the activation of myosin filaments in heart muscle.The Journal of physiology · 2024Article
- Reassessing the unifying hypothesis for hypercontractility caused by myosin mutations in hypertrophic cardiomyopathy.The EMBO journal · 2024Review
- Cardiac myosin binding protein-C phosphorylation as a function of multiple protein kinase and phosphatase activities.Nature communications · 2024Article
- Fine tuning contractility: atrial sarcomere function in health and disease.American journal of physiology. Heart and circulatory physiology · 2024Review
- Structure of mavacamten-free human cardiac thick filaments within the sarcomere by cryoelectron tomography.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mechanism-based myofilament manipulation to treat diastolic dysfunction in HFpEF.Frontiers in physiology · 2024Review
37 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Myosin binding protein-C (MyBP-C) is a key regulatory protein in heart muscle, and mutations in the MYBPC3 gene are frequently associated with cardiomyopathy. However, the mechanism of action of MyBP-C remains poorly understood, and both activating and inhibitory effects of MyBP-C on contractility have been reported. To clarify the function of the regulatory N-terminal domains of MyBP-C, we determined their effects on the structure of thick (myosin-containing) and thin (actin-containing) filaments in intact sarcomeres of heart muscle. We used fluorescent probes on troponin C in the thin filaments and on myosin regulatory light chain in the thick filaments to monitor structural changes associated with activation of demembranated trabeculae from rat ventricle by the C1mC2 region of rat MyBP-C. C1mC2 induced larger structural changes in thin filaments than calcium activation, and these were still present when active force was blocked with blebbistatin, showing that C1mC2 directly activates the thin filaments. In contrast, structural changes in thick filaments induced by C1mC2 were smaller than those associated with calcium activation and were abolished or reversed by blebbistatin. Low concentrations of C1mC2 did not affect resting force but increased calcium sensitivity and reduced cooperativity of force and structural changes in both thin and thick filaments. These results show that the N-terminal region of MyBP-C stabilizes the ON state of thin filaments and the OFF state of thick filaments and lead to a novel hypothesis for the physiological role of MyBP-C in the regulation of cardiac contractility.
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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.