ArticleProceedings of the National Academy of Sciences of the United States of America2016
Myosin light chain phosphorylation enhances contraction of heart muscle via structural changes in both thick and thin filaments.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 135 citations in OpenAlex.
- Cross-bridge model for predicting muscle short-range stiffness during movement.PLoS computational biology · 2026Article
- Temperature dependence of activation of thick and thin filaments in skeletal and cardiac muscles.Journal of muscle research and cell motility · 2026Review
- 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
- Multi-omics Insight into Cardiac Myofibril Remodeling in Post-Prandial Burmese Pythons.bioRxiv : the preprint server for biology · 2026Article
- Human atrial skinned muscle fibers exhibit reduced length-dependent activation but show faster force development kinetics than ventricular muscle.Journal of molecular and cellular cardiology · 2026Article
- Mavacamten facilitates myosin head ON-to-OFF transitions and shortens thin filament length in relaxed mouse skeletal muscle.Physiological reports · 2025Article
- Development of bifunctional fluorescent probes and their application to α-helix labelling.Organic & biomolecular chemistry · 2025Article
- Myosin-actin crossbridge independent sarcomere length induced CaJournal of molecular and cellular cardiology · 2025Article
- 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
- Post-translational modifications of vertebrate striated muscle myosin heavy chains.Cytoskeleton (Hoboken, N.J.) · 2024Review
- Interacting myosin head dynamics and their modification by 2'-deoxy-ADP.Biophysical journal · 2024Article
- The structural and functional effects of myosin regulatory light chain phosphorylation are amplified by increases in sarcomere length and [CaThe Journal of physiology · 2024Article
- Cardiac length-dependent activation driven by force-dependent thick-filament dynamics.Biophysical journal · 2024Article
- Carvedilol Activates a Myofilament Signaling Circuitry to Restore Cardiac Contractility in Heart Failure.JACC. Basic to translational science · 2024Article
- Abnormal phosphorylation / dephosphorylation and CaHeart failure reviews · 2024Review
- The selective serotonin reuptake inhibitor paroxetine improves right ventricular systolic function in experimental pulmonary hypertension.Journal of molecular and cellular cardiology plus · 2024Article
- Nanofiber-microwell cell culture system for spatially patterned differentiation of pluripotent stem cells in 3D.Materials today. Bio · 2024Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
Contraction of heart muscle is triggered by calcium binding to the actin-containing thin filaments but modulated by structural changes in the myosin-containing thick filaments. We used phosphorylation of the myosin regulatory light chain (cRLC) by the cardiac isoform of its specific kinase to elucidate mechanisms of thick filament-mediated contractile regulation in demembranated trabeculae from the rat right ventricle. cRLC phosphorylation enhanced active force and its calcium sensitivity and altered thick filament structure as reported by bifunctional rhodamine probes on the cRLC: the myosin head domains became more perpendicular to the filament axis. The effects of cRLC phosphorylation on thick filament structure and its calcium sensitivity were mimicked by increasing sarcomere length or by deleting the N terminus of the cRLC. Changes in thick filament structure were highly cooperative with respect to either calcium concentration or extent of cRLC phosphorylation. Probes on unphosphorylated myosin heads reported similar structural changes when neighboring heads were phosphorylated, directly demonstrating signaling between myosin heads. Moreover probes on troponin showed that calcium sensitization by cRLC phosphorylation is mediated by the thin filament, revealing a signaling pathway between thick and thin filaments that is still present when active force is blocked by Blebbistatin. These results show that coordinated and cooperative structural changes in the thick and thin filaments are fundamental to the physiological regulation of contractility in the heart. This integrated dual-filament concept of contractile regulation may aid understanding of functional effects of mutations in the protein components of both filaments associated with heart disease.
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