ArticleArchives of biochemistry and biophysics2014
In vitro rescue study of a malignant familial hypertrophic cardiomyopathy phenotype by pseudo-phosphorylation of myosin regulatory light chain.
Article in Archives of biochemistry and biophysics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Actomyosin-Based Nanodevices for Sensing and Actuation: Bridging Biology and Bioengineering.Biosensors · 2025Review
- Mechanistic basis for rescuing hypertrophic cardiomyopathy with myosin regulatory light chain phosphorylation.Cytoskeleton (Hoboken, N.J.) · 2024Article
- The biochemically defined super relaxed state of myosin-A paradox.The Journal of biological chemistry · 2024Article
- Phosphorylation Mimetic of Myosin Regulatory Light Chain Mitigates Cardiomyopathy-Induced Myofilament Impairment in Mouse Models of RCM and DCM.Life (Basel, Switzerland) · 2023Article
- NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart.Nature communications · 2022Article
- Molecular basis of force-pCa relation inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Functional comparison of phosphomimetic S15D and T160D mutants of myosin regulatory light chain exchanged in cardiac muscle preparations of HCM and WT mice.Frontiers in cardiovascular medicine · 2022Article
- Insights into myosin regulatory and essential light chains: a focus on their roles in cardiac and skeletal muscle function, development and disease.Journal of muscle research and cell motility · 2020Article
- Therapeutic potential of AAV9-S15D-RLC gene delivery in humanized MYL2 mouse model of HCM.Journal of molecular medicine (Berlin, Germany) · 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
- Phosphomimetic-mediated in vitro rescue of hypertrophic cardiomyopathy linked to R58Q mutation in myosin regulatory light chain.The FEBS journal · 2019Article
- ACE-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart.Scientific reports · 2018Article
- Phenotyping cardiomyopathy in adult zebrafish.Progress in biophysics and molecular biology · 2018Review
- Genetic association between 1425G/A SNP in PRKCH and hypertrophic cardiomyopathy in a Chinese population.Oncotarget · 2017Article
- Pseudophosphorylation of cardiac myosin regulatory light chain: a promising new tool for treatment of cardiomyopathy.Biophysical reviews · 2017Review
- Phosphorylation of the regulatory light chain of myosin in striated muscle: methodological perspectives.European biophysics journal : EBJ · 2016Review
- Molecular and Functional Effects of a Splice Site Mutation in the MYL2 Gene Associated with Cardioskeletal Myopathy and Early Cardiac Death in Infants.Frontiers in physiology · 2016Article
- Should we treat heart failure with phosphatase inhibitors? Better to start at the end.Journal of molecular and cellular cardiology · 2015Article
- Myosin regulatory light chain phosphorylation enhances cardiac β-myosin in vitro motility under load.Archives of biochemistry and biophysics · 2015Article
- Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pseudo-phosphorylation of cardiac myosin regulatory light chain (RLC) has never been examined as a rescue method to alleviate a cardiomyopathy phenotype brought about by a disease causing mutation in the myosin RLC. This study focuses on the aspartic acid to valine substitution (D166V) in the myosin RLC shown to be associated with a malignant phenotype of familial hypertrophic cardiomyopathy (FHC). The mutation has also been demonstrated to cause severe functional abnormalities in transgenic mice expressing D166V in the heart. To explore this novel rescue strategy, pseudo-phosphorylation of D166V was used to determine whether the D166V-induced detrimental phenotype could be brought back to the level of wild-type (WT) RLC. The S15D substitution at the phosphorylation site of RLC was inserted into the recombinant WT and D166V mutant to mimic constitutively phosphorylated RLC proteins. Non-phosphorylatable (S15A) constructs were used as controls. A multi-faceted approach was taken to determine the effect of pseudo-phosphorylation on the ability of myosin to generate force and motion. Using mutant reconstituted porcine cardiac muscle preparations, we showed an S15D-induced rescue of both the enzymatic and binding properties of D166V-myosin to actin. A significant increase in force production capacity was noted in the in vitro motility assays for S15D-D166V vs. D166V reconstituted myosin. A similar pseudo-phosphorylation induced effect was observed on the D166V-elicited abnormal Ca(2+) sensitivity of force in porcine papillary muscle strips reconstituted with phosphomimic recombinant RLCs. Results from this study demonstrate a novel in vitro rescue strategy that could be utilized in vivo to ameliorate a malignant cardiomyopathic phenotype. We show for the first time that pseudo-RLC phosphorylation can reverse the majority of the mutation-induced phenotypes highlighting the importance of RLC phosphorylation in combating cardiac disease.
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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.