ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
The immunoglobulin domain of the sodium channel β3 subunit contains a surface-localized disulfide bond that is required for homophilic binding.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Identification of Glycoprotein Biomarkers in Breast Cancer by MALDI.Life (Basel, Switzerland) · 2026Review
- New focus on cardiac voltage-gated sodium channel β1 and β1B: Novel targets for treating and understanding arrhythmias?Heart rhythm · 2025Review
- Sodium Channel β Subunits-An Additional Element in Animal Tetrodotoxin Resistance?International journal of molecular sciences · 2024Article
- Voltage-gated sodium channels: from roles and mechanisms in the metastatic cell behavior to clinical potential as therapeutic targets.Frontiers in pharmacology · 2023Review
- Intramolecular Disulfide Bonds for Biogenesis of CALHM1 Ion Channel Are Dispensable for Voltage-Dependent ActivationMolecules and cells · 2021Article
- Molecular Pathology of Sodium Channel Beta-Subunit Variants.Frontiers in pharmacology · 2021Article
- Comprehensive Analysis of Genes Associated With Sudden Infant Death Syndrome.Frontiers in pediatrics · 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
- Supramolecular clustering of the cardiac sodium channel Nav1.5 in HEK293F cells, with and without the auxiliary β3-subunit.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Gating control of the cardiac sodium channel Nav1.5 by its β3-subunit involves distinct roles for a transmembrane glutamic acid and the extracellular domain.The Journal of biological chemistry · 2019Article
- Contribution of voltage-gated sodium channel β-subunits to cervical cancer cells metastatic behavior.Cancer cell international · 2019Article
- 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
- Mechanisms of noncovalent β subunit regulation of NaThe Journal of general physiology · 2017Article
- Characterization of specific allosteric effects of the NaEuropean biophysics journal : EBJ · 2017Article
- Voltage-Gated Na+ Channels: Not Just for Conduction.Cold Spring Harbor perspectives in biology · 2016Review
- Sodium channel β subunits: emerging targets in channelopathies.Annual review of physiology · 2015Review
- A new look at sodium channel β subunits.Open biology · 2015Review
- Dual roles of voltage-gated sodium channels in development and cancer.The International journal of developmental biology · 2015Review
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9 authors.
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Abstract
The β subunits of voltage-gated sodium (Na(v)) channels possess an extracellular immunoglobulin (Ig) domain that is related to the L1 family of cell-adhesion molecules (CAMs). Here we show that in HEK293 cells, secretion of the free Ig domain of the β3 subunit is reduced significantly when it is coexpressed with the full-length β3 and β1 subunits but not with the β2 subunit. Using immunoprecipitation, we show that the β3 subunit can mediate trans homophilic-binding via its Ig domain and that the β3-Ig domain can associate heterophilically with the β1 subunit. Evolutionary tracing analysis and structural modeling identified a cluster of surface-localized amino acids fully conserved between the Ig domains of all known β3 and β1 sequences. A notable feature of this conserved surface cluster is the presence of two adjacent cysteine residues that previously we have suggested may form a disulfide bond. We now confirm the presence of the disulfide bond in β3 using mass spectrometry, and we show that its integrity is essential for the association of the full-length, membrane-anchored β3 subunit with itself. However, selective reduction of this surface disulfide bond did not inhibit homophilic binding of the purified β3-Ig domain in free solution. Hence, the disulfide bond itself is unlikely to be part of the homophilic binding site. Rather, we suggest that its integrity ensures the Ig domain of the membrane-tethered β3 subunit adopts the correct orientation for productive association to occur in vivo.
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