ArticleJournal of cell science2022
CPVT-associated calmodulin variants N53I and A102V dysregulate Ca2+ signalling via different mechanisms.
Article in Journal of cell science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Calcium signaling and postsynaptic density dynamics: the roles of calmodulin in synaptic protein regulation.Frontiers in molecular neuroscience · 2026Review
- Calmodulin D133H Disrupts CaCells · 2025Article
- Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated CaActa physiologica (Oxford, England) · 2025Article
- Calcium Role in Gap Junction Channel Gating: Direct Electrostatic or Calmodulin-Mediated?International journal of molecular sciences · 2024Review
- Identifying Key Binding Interactions Between the Cardiac L-Type Calcium Channel and Calmodulin Using Molecular Dynamics Simulations.The journal of physical chemistry. B · 2024Article
- High-affinity tuning of single fluorescent protein-type indicators by flexible linker length optimization in topology mutant.Communications biology · 2024Article
- Primary Electrical Heart Disease-Principles of Pathophysiology and Genetics.International journal of molecular sciences · 2024Review
- Calmodulin Mutations in Human Disease.Channels (Austin, Tex.) · 2023Review
- Long QT syndrome-associated calmodulin variants disrupt the activity of the slowly activating delayed rectifier potassium channel.The Journal of physiology · 2023Article
- Basic Research Approaches to Evaluate Cardiac Arrhythmia in Heart Failure and Beyond.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited condition that can cause fatal cardiac arrhythmia. Human mutations in the Ca2+ sensor calmodulin (CaM) have been associated with CPVT susceptibility, suggesting that CaM dysfunction is a key driver of the disease. However, the detailed molecular mechanism remains unclear. Focusing on the interaction with the cardiac ryanodine receptor (RyR2), we determined the effect of CPVT-associated variants N53I and A102V on the structural characteristics of CaM and on Ca2+ fluxes in live cells. We provide novel data showing that interaction of both Ca2+/CaM-N53I and Ca2+/CaM-A102V with the RyR2 binding domain is decreased. Ca2+/CaM-RyR23583-3603 high-resolution crystal structures highlight subtle conformational changes for the N53I variant, with A102V being similar to wild type (WT). We show that co-expression of CaM-N53I or CaM-A102V with RyR2 in HEK293 cells significantly increased the duration of Ca2+ events; CaM-A102V exhibited a lower frequency of Ca2+ oscillations. In addition, we show that CaMKIIδ (also known as CAMK2D) phosphorylation activity is increased for A102V, compared to CaM-WT. This paper provides novel insight into the molecular mechanisms of CPVT-associated CaM variants and will facilitate the development of strategies for future therapies.
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