ArticleJournal of the American Society of Nephrology : JASN2010
Endothelin-1 inhibits the epithelial Na+ channel through betaPix/14-3-3/Nedd4-2.
Article in Journal of the American Society of Nephrology : JASN, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 66 citations in OpenAlex.
- Renal G protein-coupled estrogen receptor 1 regulates the epithelial sodium channel promoting natriuresis to a greater extent in females.American journal of physiology. Renal physiology · 2025Article
- G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes.Cells · 2025Review
- Functional role of histamine receptors in the renal cortical collecting duct cells.American journal of physiology. Cell physiology · 2022Article
- Article
- Integrin-mediated adhesions in regulation of cellular senescence.Science advances · 2020Article
- AMPK phosphorylation of the βAmerican journal of physiology. Renal physiology · 2019Article
- Salt-deficient diet exacerbates cystogenesis in ARPKD via epithelial sodium channel (ENaC).EBioMedicine · 2019Article
- Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension.Physiological reviews · 2019Review
- Characterization of purinergic receptor expression in ARPKD cystic epithelia.Purinergic signalling · 2018Article
- βThe Journal of biological chemistry · 2018Article
- Acute In Vivo Analysis of ATP Release in Rat Kidneys in Response to Changes of Renal Perfusion Pressure.Journal of the American Heart Association · 2017Article
- Involvement of ENaC in the development of salt-sensitive hypertension.American journal of physiology. Renal physiology · 2017Review
- Endothelin-1 mediates natriuresis but not polyuria during vitamin D-induced acute hypercalcaemia.The Journal of physiology · 2017Article
- Characterization of flow-regulated cortical collecting duct endothelin-1 production.Physiological reports · 2017Article
- Renal sodium transport in renin-deficient Dahl salt-sensitive rats.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2016Article
- Dual inhibition of renin-angiotensin-aldosterone system and endothelin-1 in treatment of chronic kidney disease.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Review
- Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium.Journal of visualized experiments : JoVE · 2015Article
- Downregulation of urea transporter UT-A1 activity by 14-3-3 protein.American journal of physiology. Renal physiology · 2015Article
- βENaC acts as a mechanosensor in renal vascular smooth muscle cells that contributes to renal myogenic blood flow regulation, protection from renal injury and hypertension.Journal of nephrology research · 2015Article
- Endothelin Blockade in Diabetic Kidney Disease.Journal of clinical medicine · 2015Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Epithelial Na+ channels (ENaCs) mediate sodium reabsorption in the cortical collecting duct (CCD), but the regulatory pathways that modulate the activity of these channels are incompletely understood. Here, we observed that endothelin-1 (ET-1) attenuates ENaC activity acutely by reducing the channel's open probability and chronically by decreasing the number of channels in the plasma membrane. To investigate whether beta1Pix, a signaling protein activated by ET-1, mediates ENaC activity, we reconstituted ENaC in CHO cells with or without coexpressed beta1Pix and found that beta1Pix negatively regulates ENaC. Knockdown of betaPix in native principal cells abolished the ET-1-induced decrease in ENaC channel number. Furthermore, we found that betaPix does not decrease ENaC activity through its guanine nucleotide exchange factor (GEF) activity for Rac1 and Cdc42. Instead, coexpression of beta1Pix mutant constructs revealed that beta1Pix affects ENaC activity through binding 14-3-3 proteins. Coimmunoprecipitation experiments supported a physical interaction between beta1Pix and 14-3-3beta in cultured principal cells. Coexpression of 14-3-3beta increased ENaC activity in CHO cells, but concomitant expression of beta1Pix attenuated this increase. Recruitment of 14-3-3beta by beta1Pix impaired the interaction of 14-3-3beta with the ubiquitin ligase Nedd4-2, thereby promoting ubiquitination and degradation of ENaC. Taken together, these results suggest that the inhibitory effects of chronic ET-1 on ENaC result from betaPix interacting with the 14-3-3/Nedd4-2 pathway.
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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.