ArticleThe Journal of biological chemistry2012
Identification of the cysteine residue responsible for disulfide linkage of Na+ channel α and β2 subunits.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Neuromodulation of voltage-gated sodium channels by Gβ1γ2 subunits: Implications for GNB1-linked encephalopathy.Neurobiology of disease · 2025Article
- Short Peptides from Asian Scorpions: Bioactive Molecules with Promising Therapeutic Potential.Toxins · 2025Review
- New focus on cardiac voltage-gated sodium channel β1 and β1B: Novel targets for treating and understanding arrhythmias?Heart rhythm · 2025Review
- Article
- A method to analyze gene expression profiles from hippocampal neurons electrophysiologically recordedFrontiers in neuroscience · 2024Article
- A Push-Pull Mechanism Between PRRT2 and β4-subunit Differentially Regulates Membrane Exposure and Biophysical Properties of NaV1.2 Sodium Channels.Molecular neurobiology · 2023Article
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Intramolecular Disulfide Bonds for Biogenesis of CALHM1 Ion Channel Are Dispensable for Voltage-Dependent ActivationMolecules and cells · 2021Article
- A novel gain-of-function sodium channel β2 subunit mutation in idiopathic small fiber neuropathy.Journal of neurophysiology · 2021Article
- The Voltage-Gated Sodium Channel Beta4 Subunit Maintains Epithelial Phenotype in Mammary Cells.Cells · 2021Article
- Chemometric Models of Differential Amino Acids at the NaMolecules (Basel, Switzerland) · 2020Article
- Cell-Adhesion Properties of β-Subunits in the Regulation of Cardiomyocyte Sodium Channels.Biomolecules · 2020Review
- The voltage-gated sodium channel inhibitor, 4,9-anhydrotetrodotoxin, blocks human NaNeuroscience letters · 2020Article
- Computational Investigation of Voltage-Gated Sodium Channel β3 Subunit Dynamics.Frontiers in molecular biosciences · 2020Article
- Article
- Trafficking and Function of the Voltage-Gated Sodium Channel β2 Subunit.Biomolecules · 2019Review
- Voltage-gated sodium currents in cerebellar Purkinje neurons: functional and molecular diversity.Cellular and molecular life sciences : CMLS · 2018Review
- Voltage-gated sodium channel β subunits: The power outside the pore in brain development and disease.Neuropharmacology · 2018Review
- Voltage-Gated Sodium Channel β1/β1B Subunits Regulate Cardiac Physiology and Pathophysiology.Frontiers in physiology · 2018Review
- Voltage-Gated Sodium Channel β Subunits and Their Related Diseases.Handbook of experimental pharmacology · 2018Review
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Authors and funding
8 authors.
Funding
Abstract
Voltage-gated Na(+) channels in the brain are composed of a single pore-forming α subunit, one non-covalently linked β subunit (β1 or β3), and one disulfide-linked β subunit (β2 or β4). The final step in Na(+) channel biosynthesis in central neurons is concomitant α-β2 disulfide linkage and insertion into the plasma membrane. Consistent with this, Scn2b (encoding β2) null mice have reduced Na(+) channel cell surface expression in neurons, and action potential conduction is compromised. Here we generated a series of mutant β2 cDNA constructs to investigate the cysteine residue(s) responsible for α-β2 subunit covalent linkage. We demonstrate that a single cysteine-to-alanine substitution at extracellular residue Cys-26, located within the immunoglobulin (Ig) domain, abolishes the covalent linkage between α and β2 subunits. Loss of α-β2 covalent complex formation disrupts the targeting of β2 to nodes of Ranvier in a myelinating co-culture system and to the axon initial segment in primary hippocampal neurons, suggesting that linkage with α is required for normal β2 subcellular localization in vivo. WT β2 subunits are resistant to live cell Triton X-100 detergent extraction from the hippocampal axon initial segment, whereas mutant β2 subunits, which cannot form disulfide bonds with α, are removed by detergent. Taken together, our results demonstrate that α-β2 covalent association via a single, extracellular disulfide bond is required for β2 targeting to specialized neuronal subcellular domains and for β2 association with the neuronal cytoskeleton within those domains.
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