ArticleThe Journal of biological chemistry
Inhibition of the epithelial sodium channel (ENaC) by connexin 30 involves stimulation of clathrin-mediated endocytosis.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Analysis of sodium self-inhibition of the epithelial sodium channel (ENaC) using classical and medium-throughput automated two-electrode voltage-clamp recordings.Pflugers Archiv : European journal of physiology · 2026Article
- Acute activation of human epithelial sodium channel (ENaC) by serum and glucocorticoid inducible kinase 1 (SGK1) requires prior cleavage of the channel's γ-subunit at its proximal cleavage site.Pflugers Archiv : European journal of physiology · 2025Article
- SECS, drugs, and Rac1&Rho: regulation of EnNaC in vascular endothelial cells.Pflugers Archiv : European journal of physiology · 2025Article
- Ion channel function of polycystin-2/polycystin-1 heteromer revealed by structure-guided mutagenesis.FEBS letters · 2025Article
- Automated patch-clamp recordings for detecting activators and inhibitors of the epithelial sodium channel (ENaC).Pflugers Archiv : European journal of physiology · 2025Article
- Transmembrane Serine Protease 2 and Proteolytic Activation of the Epithelial Sodium Channel in Mouse Kidney.Journal of the American Society of Nephrology : JASN · 2025Article
- Disease-associated missense mutations in the pore loop of polycystin-2 alter its ion channel function in a heterologous expression system.The Journal of biological chemistry · 2024Article
- The small molecule activator S3969 stimulates the epithelial sodium channel by interacting with a specific binding pocket in the channel's β-subunit.The Journal of biological chemistry · 2024Article
- The Epithelial Sodium Channel-An Underestimated Drug Target.International journal of molecular sciences · 2023Review
- Two adjacent phosphorylation sites in the C-terminus of the channel's α-subunit have opposing effects on epithelial sodium channel (ENaC) activity.Pflugers Archiv : European journal of physiology · 2022Article
- Transmembrane serine protease 2 (TMPRSS2) proteolytically activates the epithelial sodium channel (ENaC) by cleaving the channel's γ-subunit.The Journal of biological chemistry · 2022Article
- The Effect of Dynasore Upon the Negative Interaction Between ENaC and CFTR Channels in Xenopus laevis Oocytes.The Journal of membrane biology · 2022Article
- Proteolytic activation of the epithelial sodium channel (ENaC) by factor VII activating protease (FSAP) and its relevance for sodium retention in nephrotic mice.Pflugers Archiv : European journal of physiology · 2022Article
- A polycystin-2 protein with modified channel properties leads to an increased diameter of renal tubules and to renal cysts.Journal of cell science · 2021Article
- Zymogen-locked mutant prostasin (Prss8) leads to incomplete proteolytic activation of the epithelial sodium channel (ENaC) and severely compromises triamterene tolerance in mice.Acta physiologica (Oxford, England) · 2021Article
- Essential requirement of complex number for oscillatory phenomenon in intracellular trafficking process.Computational and structural biotechnology journal · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Mice lacking connexin 30 (Cx30) display increased epithelial sodium channel (ENaC) activity in the distal nephron and develop salt-sensitive hypertension. This indicates a functional link between Cx30 and ENaC, which remains incompletely understood. Here, we explore the effect of Cx30 on ENaC function using the Xenopus laevis oocyte expression system. Coexpression of human Cx30 with human αβγENaC significantly reduced ENaC-mediated whole-cell currents. The size of the inhibitory effect on ENaC depended on the expression level of Cx30 and required Cx30 ion channel activity. ENaC inhibition by Cx30 was mainly due to reduced cell surface ENaC expression resulting from enhanced ENaC retrieval without discernible effects on proteolytic channel activation and single-channel properties. ENaC retrieval from the cell surface involves the interaction of the ubiquitin ligase Nedd4-2 with PPPxY-motifs in the C-termini of ENaC. Truncating the C- termini of β- or γENaC significantly reduced the inhibitory effect of Cx30 on ENaC. In contrast, mutating the prolines belonging to the PPPxY-motif in γENaC or coexpressing a dominant-negative Xenopus Nedd4 (xNedd4-CS) did not significantly alter ENaC inhibition by Cx30. Importantly, the inhibitory effect of Cx30 on ENaC was significantly reduced by Pitstop-2, an inhibitor of clathrin-mediated endocytosis, or by mutating putative clathrin adaptor protein 2 (AP-2) recognition motifs (YxxФ) in the C termini of β- or γ-ENaC. In conclusion, our findings suggest that Cx30 inhibits ENaC by promoting channel retrieval from the plasma membrane via clathrin-dependent endocytosis. Lack of this inhibition may contribute to increased ENaC activity and salt-sensitive hypertension in mice with Cx30 deficiency.
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