ArticlePloS one2017
CPVT-associated cardiac ryanodine receptor mutation G357S with reduced penetrance impairs Ca2+ release termination and diminishes protein expression.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed.
- Long-Term Serial Exercise Stress Testing in Catecholaminergic Polymorphic Ventricular Tachycardia on Beta-Blocker and Flecainide Therapy.Journal of cardiovascular electrophysiology · 2026Article
- Catecholaminergic polymorphic ventricular tachycardia: A narrative review of recent advances in genetics, mechanisms, diagnosis, and treatment.Asian heart journal · 2025Review
- Phosphorylation of phospholamban promotes SERCA2a activation by dwarf open reading frame (DWORF).Cell calcium · 2024Article
- Molecular Pathways and Animal Models of Arrhythmias.Advances in experimental medicine and biology · 2024Article
- RYR2 deficient human model identifies calcium handling and metabolic dysfunction impacting pharmacological responses.Frontiers in cardiovascular medicine · 2024Article
- Disparate molecular mechanisms in cardiac ryanodine receptor channelopathies.Frontiers in molecular biosciences · 2024Article
- Correction: "Ryanopathies" and RyR2 dysfunctions: can we further decipher them using in vitro human disease models?Cell death & disease · 2022Article
- CPVT-associated calmodulin variants N53I and A102V dysregulate Ca2+ signalling via different mechanisms.Journal of cell science · 2022Article
- A novel homozygous nonsense mutation in the CA2 gene (c.368G>A, p.W123X) linked to carbonic anhydrase II deficiency syndrome in a Chinese family.Metabolic brain disease · 2021Article
- Novel RyR2 Mutation (G3118R) Is Associated With Autosomal Recessive Ventricular Fibrillation and Sudden Death: Clinical, Functional, and Computational Analysis.Journal of the American Heart Association · 2021Article
- TRIC-A Channel Maintains Store Calcium Handling by Interacting With Type 2 Ryanodine Receptor in Cardiac Muscle.Circulation research · 2020Article
- Recruiting RyRs to Open in a CaBiophysical journal · 2020Article
- Cardiac hypertrophy and arrhythmia in mice induced by a mutation in ryanodine receptor 2.JCI insight · 2019Article
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8 authors.
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Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the most lethal inherited cardiac arrhythmias mostly linked to cardiac ryanodine receptor (RyR2) mutations with high disease penetrance. Interestingly, a novel RyR2 mutation G357S discovered in a large family of more than 1400 individuals has reduced penetrance. The molecular basis for the incomplete disease penetrance in this family is unknown. To gain insights into the variable disease expression in this family, we determined the impact of the G357S mutation on RyR2 function and expression. We assessed spontaneous Ca2+ release in HEK293 cells expressing RyR2 wildtype and the G357S mutant during store Ca2+ overload, also known as store overload induced Ca2+ release (SOICR). We found that the G357S mutation reduced the percentage of RyR2-expressing cells that showed SOICR. However, in cells that displayed SOICR, G357S reduced the thresholds for the activation and termination of SOICR. Furthermore, G357S decreased the thermal stability of the N-terminal domain of RyR2, and markedly reduced the protein expression of the full-length RyR2. On the other hand, the G357S mutation did not alter the Ca2+ activation of [3H]ryanodine binding or the Ca2+ induced release of Ca2+ from the intracellular stores in HEK293 cells. These data indicate that the CPVT-associated G357S mutation enhances the arrhythmogenic SOICR and reduces RyR2 protein expression, which may be attributable to the incomplete penetrance of CPVT in this family.
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