ArticleJCI insight2021
Sodium channel β1 subunits participate in regulated intramembrane proteolysis-excitation coupling.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Nanoscale organization in the cell membrane dynamically modulates the biophysics of voltage-gated sodium channels.Nature communications · 2026Article
- Sudden death-associated KCNH2 variants exert opposing effects on a nuclear subdomain of the cardiac potassium channel hERG1.The Journal of biological chemistry · 2026Article
- A Novel Mouse Model for Developmental and Epileptic Encephalopathy by Purkinje Cell-Specific Deletion ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Ataxia and cerebellar hypoexcitability in a mouse model of SCN1B-linked Dravet syndrome.JCI insight · 2025Article
- Altered cardiac excitability and arrhythmia in models of SCN1B-linked developmental and epileptic encephalopathy.JCI insight · 2025Article
- Voltage-Gated Sodium Channel Dysfunction in Epilepsy: Zebrafish Models for Therapeutics.Biomedicines · 2025Review
- The α/β3 complex of human voltage-gated sodium channel hNaJournal of molecular modeling · 2025Article
- New focus on cardiac voltage-gated sodium channel β1 and β1B: Novel targets for treating and understanding arrhythmias?Heart rhythm · 2025Review
- Decreased ability to manage increases in reactive oxygen species may underlie susceptibility to arrhythmias in mice lackingAmerican journal of physiology. Heart and circulatory physiology · 2024Article
- Development and characterization of the mode-of-action of inhibitory and agonist peptides targeting the voltage-gated sodium channel SCN1B beta-subunit.Journal of molecular and cellular cardiology · 2024Article
- Altered cardiac energetics in mice lacking Scn1b.Cardiovascular research · 2024Article
- Physical and functional convergence of the autism risk genes Scn2a and Ank2 in neocortical pyramidal cell dendrites.Neuron · 2024Article
- Complex Synaptic and Intrinsic Interactions Disrupt Input/Output Functions in the Hippocampus ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Article
- Epilepsy and sudden unexpected death in epilepsy in a mouse model of humanBrain communications · 2023Article
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- Article
- Neonatal Scn1b-null mice have sinoatrial node dysfunction, altered atrial structure, and atrial fibrillation.JCI insight · 2022Article
- A single injection of periostin decreases cardiac voltage-gated NaThe Journal of veterinary medical science · 2021Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Loss-of-function (LOF) variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are linked to human diseases with high risk of sudden death, including developmental and epileptic encephalopathy and cardiac arrhythmia. β1 Subunits modulate the cell-surface localization, gating, and kinetics of sodium channel pore-forming α subunits. They also participate in cell-cell and cell-matrix adhesion, resulting in intracellular signal transduction, promotion of cell migration, calcium handling, and regulation of cell morphology. Here, we investigated regulated intramembrane proteolysis (RIP) of β1 by BACE1 and γ-secretase and show that β1 subunits are substrates for sequential RIP by BACE1 and γ-secretase, resulting in the generation of a soluble intracellular domain (ICD) that is translocated to the nucleus. Using RNA sequencing, we identified a subset of genes that are downregulated by β1-ICD overexpression in heterologous cells but upregulated in Scn1b-null cardiac tissue, which lacks β1-ICD signaling, suggesting that the β1-ICD may normally function as a molecular brake on gene transcription in vivo. We propose that human disease variants resulting in SCN1B LOF cause transcriptional dysregulation that contributes to altered excitability. Moreover, these results provide important insights into the mechanism of SCN1B-linked channelopathies, adding RIP-excitation coupling to the multifunctionality of sodium channel β1 subunits.
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Registered trials
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