ArticleThe Journal of clinical investigation2012
Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease.
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 107 papers.
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Who cites it
107 citing papers in PubMed, 144 citations in OpenAlex.
- Potential roles for transient receptor potential vanilloid 1 in heart failure with preserved ejection fraction.Channels (Austin, Tex.) · 2026Review
- Environmental cues signal through circadian control of sarcomeric gene expression during cardiomyocyte hypertrophy.Epigenetics · 2026Article
- Biomolecular condensation of cMLCK enables myosin motor phosphorylation in the heart.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
- Myocardial transcriptomic and proteomic landscapes across the menopausal continuum in a murine model of chemically induced accelerated ovarian failure.Physiological genomics · 2025Article
- Maturation of human cardiac organoids enables complex disease modeling and drug discovery.Nature cardiovascular research · 2025Article
- Carvedilol Activates a Myofilament Signaling Circuitry to Restore Cardiac Contractility in Heart Failure.JACC. Basic to translational science · 2024Article
- The ric-8b protein (resistance to inhibitors of cholinesterase 8b) is key to preserving contractile function in the adult heart.The Journal of biological chemistry · 2024Article
- Fine tuning contractility: atrial sarcomere function in health and disease.American journal of physiology. Heart and circulatory physiology · 2024Review
- PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation.Circulation research · 2023Article
- Torsional and strain dysfunction precede overt heart failure in a mouse model of dilated cardiomyopathy pathogenesis.American journal of physiology. Heart and circulatory physiology · 2023Article
- RLC phosphorylation amplifies Ca2+ sensitivity of force in myocardium from cMyBP-C knockout mice.The Journal of general physiology · 2023Article
- Beyond CFD: Emerging methodologies for predictive simulation in cardiovascular health and disease.Biophysics reviews · 2023Review
- Cardiac Sarcomere Signaling in Health and Disease.International journal of molecular sciences · 2022Review
- Molecular regulation of stretch activation.American journal of physiology. Cell physiology · 2022Article
- Sarcomere maturation: function acquisition, molecular mechanism, and interplay with other organelles.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart.Nature communications · 2022Article
- Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy.Circulation · 2022Article
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Subcellular Remodeling in Filamin C Deficient Mouse Hearts Impairs Myocyte Tension Development during Progression of Dilated Cardiomyopathy.International journal of molecular sciences · 2022Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
Actin-myosin interactions provide the driving force underlying each heartbeat. The current view is that actin-bound regulatory proteins play a dominant role in the activation of calcium-dependent cardiac muscle contraction. In contrast, the relevance and nature of regulation by myosin regulatory proteins (for example, myosin light chain-2 [MLC2]) in cardiac muscle remain poorly understood. By integrating gene-targeted mouse and computational models, we have identified an indispensable role for ventricular Mlc2 (Mlc2v) phosphorylation in regulating cardiac muscle contraction. Cardiac myosin cycling kinetics, which directly control actin-myosin interactions, were directly affected, but surprisingly, Mlc2v phosphorylation also fed back to cooperatively influence calcium-dependent activation of the thin filament. Loss of these mechanisms produced early defects in the rate of cardiac muscle twitch relaxation and ventricular torsion. Strikingly, these defects preceded the left ventricular dysfunction of heart disease and failure in a mouse model with nonphosphorylatable Mlc2v. Thus, there is a direct and early role for Mlc2 phosphorylation in regulating actin-myosin interactions in striated muscle contraction, and dephosphorylation of Mlc2 or loss of these mechanisms can play a critical role in heart failure.
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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.