ArticleHuman molecular genetics2021
Ryanodine receptor remodeling in cardiomyopathy and muscular dystrophy caused by lamin A/C gene mutation.
Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- An Unbiased Drug Screen in a Drosophila Model ofInternational journal of molecular sciences · 2026Article
- Simtuzumab Attenuates Loxl2-Mediated Extracellular Matrix Remodeling and Preserves Cardiac Function inCirculation. Heart failure · 2026Article
- An integrative approach to identify novel miRNA-mRNA interaction networks in LMNA-cardiomyopathy.Scientific reports · 2026Article
- Structural basis for simvastatin-induced skeletal muscle weakness associated with type 1 ryanodine receptor T4709M mutation.The Journal of clinical investigation · 2025Article
- Calcium handling remodeling in dilated cardiomyopathy: From molecular mechanisms to targeted therapies.Channels (Austin, Tex.) · 2025Review
- Dysferlin and the Regulation of CaCells · 2025Review
- Functional Foods, a Hope to Delay Muscle Dystrophy Progression: A Potential Role for Omega Fatty Acids.Nutrients · 2025Review
- Structural basis for ryanodine receptor type 2 leak in heart failure and arrhythmogenic disorders.Nature communications · 2024Article
- Global Proteomic Analysis Reveals Alterations in Differentially Expressed Proteins between Cardiopathic Lamin A/C Mutations.Journal of proteome research · 2024Article
- mTOR Inhibition Prolongs Survival and Has Beneficial Effects on Heart Function After Onset of Lamin A/C Gene Mutation Cardiomyopathy in Mice.Circulation. Heart failure · 2024Article
- Personalized medicine in the dish to prevent calcium leak associated with short-coupled polymorphic ventricular tachycardia in patient-derived cardiomyocytes.Stem cell research & therapy · 2023Article
- Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart.Biomolecules · 2023Review
- Heart failure-induced cognitive dysfunction is mediated by intracellular CaNature neuroscience · 2023Article
- Impaired Cardiomyocyte Maturation Leading to DCM: A Case Report and Literature Review.Medicina (Kaunas, Lithuania) · 2023Review
- Roles of the cytoskeleton in human diseases.Molecular biology reports · 2023Review
- Development of Ryanodine Receptor (RyR) Inhibitors for Skeletal Muscle and Heart Diseases.Juntendo Iji zasshi = Juntendo medical journal · 2023Article
- Native lamin A/C proteomes and novel partners from heart and skeletal muscle in a mouse chronic inflammation model of human frailty.Frontiers in cell and developmental biology · 2023Article
- Article
- Alzheimer's-like signaling in brains of COVID-19 patients.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Pro-inflammatory cytokines as emerging molecular determinants in cardiolaminopathies.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutations in the lamin A/C gene (LMNA), which encodes A-type lamins, cause several diseases called laminopathies, the most common of which is dilated cardiomyopathy with muscular dystrophy. The role of Ca2+ regulation in these diseases remain poorly understood. We now show biochemical remodeling of the ryanodine receptor (RyR)/intracellular Ca2+ release channel in heart samples from human subjects with LMNA mutations, including protein kinase A-catalyzed phosphorylation, oxidation and depletion of the stabilizing subunit calstabin. In the LmnaH222P/H222P murine model of Emery-Dreifuss muscular dystrophy caused by LMNA mutation, we demonstrate an age-dependent biochemical remodeling of RyR2 in the heart and RyR1 in skeletal muscle. This RyR remodeling is associated with heart and skeletal muscle dysfunction. Defective heart and muscle function are ameliorated by treatment with a novel Rycal small molecule drug (S107) that fixes 'leaky' RyRs. SMAD3 phosphorylation is increased in hearts and diaphragms of LmnaH222P/H222P mice, which enhances NADPH oxidase binding to RyR channels, contributing to their oxidation. There is also increased generalized protein oxidation, increased calcium/calmodulin-dependent protein kinase II-catalyzed phosphorylation of RyRs and increased protein kinase A activity in these tissues. Our data show that RyR remodeling plays a role in cardiomyopathy and skeletal muscle dysfunction caused by LMNA mutation and identify these Ca2+ channels as a potential therapeutic target.
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