ArticleChannels (Austin, Tex.)
Activation of the epithelial sodium channel by the metalloprotease meprin β subunit.
Article in Channels (Austin, Tex.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Phospholipase AThe journal of venomous animals and toxins including tropical diseases · 2025Article
- Epithelial NaComprehensive Physiology · 2024Review
- ENaC activation by proteases.Acta physiologica (Oxford, England) · 2022Review
- Comparative compositional and functional venomic profiles among venom specimens from juvenile, subadult and adult Russell's viper (The journal of venomous animals and toxins including tropical diseases · 2022Article
- To be there when the picture is being painted.The Journal of biological chemistry · 2020Article
- The pathophysiological effects of Russell's viper (Toxicon: X · 2020Article
- Regulating ENaC's gate.American journal of physiology. Cell physiology · 2020Review
- Proteases: History, discovery, and roles in health and disease.The Journal of biological chemistry · 2019Review
- The function and regulation of acid-sensing ion channels (ASICs) and the epithelial Na(+) channel (ENaC): IUPHAR Review 19.British journal of pharmacology · 2016Review
- Sodium retention and volume expansion in nephrotic syndrome: implications for hypertension.Advances in chronic kidney disease · 2015Review
- Diverse impact of acute and long-term extracellular proteolytic activity on plasticity of neuronal excitability.Frontiers in cellular neuroscience · 2015Review
- Epithelial Sodium Channel-Mediated Sodium Transport Is Not Dependent on the Membrane-Bound Serine Protease CAP2/Tmprss4.PloS one · 2015Article
- Demonstration of proteolytic activation of the epithelial sodium channel (ENaC) by combining current measurements with detection of cleavage fragments.Journal of visualized experiments : JoVE · 2014Article
- ADAM10 is the major sheddase responsible for the release of membrane-associated meprin A.The Journal of biological chemistry · 2014Article
- Meprin A metalloproteinase and its role in acute kidney injury.American journal of physiology. Renal physiology · 2013Review
- Proteolytic activation of the epithelial sodium channel (ENaC) by the cysteine protease cathepsin-S.Pflugers Archiv : European journal of physiology · 2012Article
- TMPRSS4-dependent activation of the epithelial sodium channel requires cleavage of the γ-subunit distal to the furin cleavage site.American journal of physiology. Renal physiology · 2012Article
- Matrix metalloproteinase-9 and -2 enhance the ligand sensitivity of photoreceptor cyclic nucleotide-gated channels.Channels (Austin, Tex.)Article
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Authors and funding
7 authors at 7 institutions in 3 countries.
Funding
Abstract
The Epithelial Na(+) Channel (ENaC) is an apical heteromeric channel that mediates Na(+) entry into epithelial cells from the luminal cell surface. ENaC is activated by proteases that interact with the channel during biosynthesis or at the extracellular surface. Meprins are cell surface and secreted metalloproteinases of the kidney and intestine. We discovered by affinity chromatography that meprins bind γ-ENaC, a subunit of the ENaC hetero-oligomer. The physical interaction involves NH(2)-terminal cytoplasmic residues 37-54 of γ-ENaC, containing a critical gating domain immediately before the first transmembrane domain, and the cytoplasmic COOH-terminal tail of meprin β (residues 679-704). This potential association was confirmed by co-expression and co-immunoprecipitation studies. Functional assays revealed that meprins stimulate ENaC expressed exogenously in Xenopus oocytes and endogenously in epithelial cells. Co-expression of ENaC subunits and meprin β or α/β in Xenopus oocytes increased amiloride-sensitive Na(+) currents approximately two-fold. This increase was blocked by preincubation with an inhibitor of meprin activity, actinonin. The meprin-mediated increase in ENaC currents in oocytes and epithelial cell monolayers required meprin β, but not the α subunit. Meprin β promoted cleavage of α and γ-ENaC subunits at sites close to the second transmembrane domain in the extracellular domain of each channel subunit. Thus, meprin β regulates the activity of ENaC in a metalloprotease-dependent fashion.
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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.