ArticleJournal of molecular and cellular cardiology2009
Regulatory light chain mutations associated with cardiomyopathy affect myosin mechanics and kinetics.
Article in Journal of molecular and cellular cardiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 62 citations in OpenAlex.
- Incomplete-penetrant hypertrophic cardiomyopathyProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Motility Assay to Probe the Calcium Sensitivity of Myosin and Regulated Thin Filaments.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Cardiac myosin contraction and mechanotransduction in health and disease.The Journal of biological chemistry · 2021Review
- Impact of regulatory light chain mutation K104E on the ATPase and motor properties of cardiac myosin.The Journal of general physiology · 2021Article
- Regulatory Light Chains in Cardiac Development and Disease.International journal of molecular sciences · 2021Review
- Mavacamten decreases maximal force and CaAmerican journal of physiology. Heart and circulatory physiology · 2021Article
- The co-segregation of the MYL2 R58Q mutation in Chinese hypertrophic cardiomyopathy family and its pathological effect on cardiomyopathy disarray.Molecular genetics and genomics : MGG · 2019Article
- Induced Pluripotent Stem Cell-Derived Cardiomyocytes from a Patient with MYL2-R58Q-Mediated Apical Hypertrophic Cardiomyopathy Show Hypertrophy, Myofibrillar Disarray, and Calcium Perturbations.Journal of cardiovascular translational research · 2019Article
- Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Hereditary heart disease: pathophysiology, clinical presentation, and animal models of HCM, RCM, and DCM associated with mutations in cardiac myosin light chains.Pflugers Archiv : European journal of physiology · 2019Review
- Slow-twitch skeletal muscle defects accompany cardiac dysfunction in transgenic mice with a mutation in the myosin regulatory light chain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Mechanistic complexity of contractile dysfunction in hypertrophic cardiomyopathy.The Journal of general physiology · 2018Article
- Genetic and Tissue Engineering Approaches to Modeling the Mechanics of Human Heart Failure for Drug Discovery.Frontiers in cardiovascular medicine · 2018Review
- Article
- Cardiac contractility, motor function, and cross-bridge kinetics in N47K-RLC mutant mice.The FEBS journal · 2017Article
- Gene expression patterns in transgenic mouse models of hypertrophic cardiomyopathy caused by mutations in myosin regulatory light chain.Archives of biochemistry and biophysics · 2016Article
- Article
- Review
- Myosin regulatory light chain phosphorylation enhances cardiac β-myosin in vitro motility under load.Archives of biochemistry and biophysics · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The myosin regulatory light chain (RLC) wraps around the alpha-helical neck region of myosin. This neck region has been proposed to act as a lever arm, amplifying small conformational changes in the myosin head to generate motion. The RLC serves an important structural role, supporting the myosin neck region and a modulatory role, tuning the kinetics of the actin myosin interaction. Given the importance of the RLC, it is not surprising that mutations of the RLC can lead to familial hypertrophic cardiomyopathy (FHC), the leading cause of sudden cardiac death in people under 30. Population studies identified two FHC mutations located near the cationic binding site of the RLC, R58Q and N47K. Although these mutations are close in sequence, they differ in clinical presentation and prognosis, with R58Q showing a more severe phenotype. We examined the molecular based changes in myosin that are responsible for the disease phenotype by purifying myosin from transgenic mouse hearts expressing mutant myosins and examining actin filament sliding using the in vitro motility assay. We found that both R58Q and N47K show reductions in force compared to the wild type that could result in compensatory hypertrophy. Furthermore, we observed a higher ATPase rate and an increased activation at submaximal calcium levels for the R58Q myosin that could lead to decreased efficiency and incomplete cardiac relaxation, potentially explaining the more severe phenotype for the R58Q mutation.
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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.