ArticleThe Journal of biological chemistry2010
Nedd4-1 and beta-arrestin-1 are key regulators of Na+/H+ exchanger 1 ubiquitylation, endocytosis, and function.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 73 citations in OpenAlex.
- Structure of NHE6 and its lipid-mediated interactions regulating endosomal pH.Nature communications · 2026Article
- PIPNature communications · 2025Article
- Novel role of GRK2 in isoprenaline-induced activation of NaMolecular biology reports · 2025Article
- Susceptibility gene identification and risk evaluation model construction by transcriptome-wide association analysis for salt sensitivity of blood pressure.BMC genomics · 2024Article
- LITAF protects against pore-forming protein-induced cell death by promoting membrane repair.Science immunology · 2024Article
- β-arrestin1 is an E3 ubiquitin ligase adaptor for substrate linear polyubiquitination.The Journal of biological chemistry · 2023Article
- α-Arrestins and Their Functions: From Yeast to Human Health.International journal of molecular sciences · 2022Review
- Review
- Alteration and dysfunction of ion channels/transporters in a hypoxic microenvironment results in the development and progression of gastric cancer.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Review
- Article
- Trafficking, localization and degradation of the NaScientific reports · 2018Article
- Compensatory Internalization of Pma1 in V-ATPase Mutants inGenetics · 2018Article
- A novel proton transfer mechanism in the SLC11 family of divalent metal ion transporters.Scientific reports · 2017Article
- The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling.Pharmacological reviews · 2017Review
- Posttranslational Regulation of Organic Anion Transporters by Ubiquitination: Known and Novel.Medicinal research reviews · 2016Review
- The role of Nedd4-1 WW domains in binding and regulating human organic anion transporter 1.American journal of physiology. Renal physiology · 2016Article
- Nedd4-2 but not Nedd4-1 is critical for protein kinase C-regulated ubiquitination, expression, and transport activity of human organic anion transporter 1.American journal of physiology. Renal physiology · 2016Article
- Mutation in the Monocarboxylate Transporter 12 Gene Affects Guanidinoacetate Excretion but Does Not Cause Glucosuria.Journal of the American Society of Nephrology : JASN · 2016Article
- The Hydroxyl Side Chain of a Highly Conserved Serine Residue Is Required for Cation Selectivity and Substrate Transport in the Glial Glutamate Transporter GLT-1/SLC1A2.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitously expressed mammalian Na(+)/H(+) exchanger 1 (NHE1) controls cell volume and pH but is also critically involved in complex biological processes like cell adhesion, cell migration, cell proliferation, and mechanosensation. Pathways controlling NHE1 turnover at the plasma membrane, however, are currently unclear. Here, we demonstrate that NHE1 undergoes ubiquitylation at the plasma membrane by a process that is unprecedented for a mammalian ion transport protein. This process requires the adapter protein β-arrestin-1 that interacts with both the E3 ubiquitin ligase Nedd4-1 and the NHE1 C terminus. Truncation of NHE1 C terminus to amino acid 550 abolishes binding to β-arrestin-1 and NHE1 ubiquitylation. Overexpression of β-arrestin-1 or of wild type but not ligase-dead Nedd4-1 increases NHE1 ubiquitylation. siRNA-mediated knock-down of Nedd4-1 or β-arrestin-1 reduces NHE1 ubiquitylation and endocytosis leading to increased NHE1 surface levels. Fibroblasts derived from β-arrestin-1 and Nedd4-1 knock-out mice show loss of NHE1 ubiquitylation, increased plasmalemmal NHE1 levels and greatly enhanced NHE1 transport compared with wild-type fibroblasts. These findings reveal Nedd4-1 and β-arrestin-1 as key regulators of NHE1 ubiquitylation, endocytosis, and function. Our data suggest a broader role for β-arrestins in the regulation of membrane ion transport proteins than currently known.
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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.