ArticleThe Journal of biological chemistry2014
Cysteine palmitoylation of the γ subunit has a dominant role in modulating activity of the epithelial sodium channel.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Post-translational protein S-palmitoylation in renal tubular injury: mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Review
- Structural insights into subunit-dependent functional regulation in epithelial sodium channels.Structure (London, England : 1993) · 2025Article
- Loss of the alpha subunit distal furin cleavage site blunts ENaC activation following NaThe Journal of physiology · 2024Article
- Epithelial NaComprehensive Physiology · 2024Review
- Mice lacking γENaC palmitoylation sites maintain benzamil-sensitive Na+ transport despite reduced channel activity.JCI insight · 2023Article
- The Epithelial Sodium Channel-An Underestimated Drug Target.International journal of molecular sciences · 2023Review
- The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis.Biomedicines · 2022Review
- Palmitoylation of Voltage-Gated Ion Channels.International journal of molecular sciences · 2022Review
- Force From Filaments: The Role of the Cytoskeleton and Extracellular Matrix in the Gating of Mechanosensitive Channels.Frontiers in cell and developmental biology · 2022Review
- Engineered mutant α-ENaC subunit mRNA delivered by lipid nanoparticles reduces amiloride currents in cystic fibrosis-based cell and mice models.Science advances · 2020Article
- ENaC in Salt-Sensitive Hypertension: Kidney and Beyond.Current hypertension reports · 2020Review
- DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels.The Journal of biological chemistry · 2020Article
- Article
- Regulating ENaC's gate.American journal of physiology. Cell physiology · 2020Review
- Murine epithelial sodium (NaThe Journal of biological chemistry · 2019Article
- New insights regarding epithelial Na+ channel regulation and its role in the kidney, immune system and vasculature.Current opinion in nephrology and hypertension · 2019Review
- Epithelial NaAnnual review of physiology · 2018Review
- Stochastic palmitoylation of accessible cysteines in membrane proteins revealed by native mass spectrometry.Nature communications · 2017Article
- Post-translational palmitoylation controls the voltage gating and lipid raft association of the CALHM1 channel.The Journal of physiology · 2017Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The epithelial sodium channel (ENaC) is composed of three homologous subunits (α, β, and γ) with cytoplasmic N and C termini. Our previous work revealed that two cytoplasmic Cys residues in the β subunit, βCys-43 and βCys-557, are Cys-palmitoylated. ENaCs with mutant βC43A/C557A exhibit normal surface expression but enhanced Na(+) self-inhibition and reduced channel open probability. Although the α subunit is not palmitoylated, we now show that the two cytoplasmic Cys residues in the γ subunit are palmitoylated. ENaCs with mutant γC33A, γC41A, or γC33A/C41A exhibit reduced activity compared with wild type channels but normal surface expression and normal levels of α and γ subunit-activating cleavage. These mutant channels have significantly enhanced Na(+) self-inhibition and reduced open probability compared with wild type ENaCs. Channel activity was enhanced by co-expression with the palmitoyltransferase DHHC2 that also co-immunoprecipitates with ENaCs. Secondary structure prediction of the N terminus of the γ subunit places γCys-33 within an α-helix and γCys-44 on a coil before the first transmembrane domain within a short tract that includes a well conserved His-Gly motif, where mutations have been associated with altered channel gating. Our current and previous results suggest that palmitoylation of the β and γ subunits of ENaCs enhances interactions of their respective cytoplasmic domains with the plasma membrane and stabilizes the open state of the channel. Comparison of activities of channels lacking palmitoylation sites in individual or multiple subunits revealed that γ subunit palmitoylation has a dominant role over β subunit palmitoylation in modulating ENaC gating.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.