ArticleThe Journal of biological chemistry2012
Unconventional chemiosmotic coupling of NHA2, a mammalian Na+/H+ antiporter, to a plasma membrane H+ gradient.
Article in The Journal of biological chemistry, 2012. 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, 40 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- pH-dependent activation of the NaNature communications · 2026Article
- Structure and Inhibition of the Human NaInternational journal of molecular sciences · 2025Article
- Residues R177 and S178 of the human NaFEBS letters · 2025Article
- Site-directed mutagenesis at the Glu78 in Ec-NhaA transporter impacting ion exchange: a biophysical study.European biophysics journal : EBJ · 2024Article
- The crossing of two unwound transmembrane regions that is the hallmark of the NhaA structural fold is critical for antiporter activity.Scientific reports · 2024Article
- Review
- NaInternational journal of molecular sciences · 2023Review
- Post-translational modification and mitochondrial function in Parkinson's disease.Frontiers in molecular neuroscience · 2023Review
- Allosteric links between the hydrophilic N-terminus and transmembrane core of human NaProtein science : a publication of the Protein Society · 2022Article
- Structure, mechanism and lipid-mediated remodeling of the mammalian NaNature structural & molecular biology · 2022Article
- The Less Well-Known Little Brothers: The SLC9B/NHA Sodium Proton Exchanger Subfamily-Structure, Function, Regulation and Potential Drug-Target Approaches.Frontiers in physiology · 2022Review
- A guide to plasma membrane solute carrier proteins.The FEBS journal · 2021Review
- Insight into the direct interaction of NaScientific reports · 2021Article
- NHA2 promotes cyst development in an in vitro model of polycystic kidney disease.The Journal of physiology · 2019Article
- The Toxicogenome of Hyalella azteca: A Model for Sediment Ecotoxicology and Evolutionary Toxicology.Environmental science & technology · 2018Article
- SLC9 Gene Family: Function, Expression, and Regulation.Comprehensive Physiology · 2018Review
- Identification of placental nutrient transporters associated with intrauterine growth restriction and pre-eclampsia.BMC genomics · 2018Article
- Lysine 300 is essential for stability but not for electrogenic transport of theThe Journal of biological chemistry · 2017Article
- NHA2 is expressed in distal nephron and regulated by dietary sodium.Journal of physiology and biochemistry · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Human NHA2, a newly discovered cation proton antiporter, is implicated in essential hypertension by gene linkage analysis. We show that NHA2 mediates phloretin-sensitive Na(+)-Li(+) counter-transport (SLC) activity, an established marker for hypertension. In contrast to bacteria and fungi where H(+) gradients drive uptake of metabolites, secondary transport at the plasma membrane of mammalian cells is coupled to the Na(+) electrochemical gradient. Our findings challenge this paradigm by showing coupling of NHA2 and V-type H(+)-ATPase at the plasma membrane of kidney-derived MDCK cells, resulting in a virtual Na(+) efflux pump. Thus, NHA2 functionally recapitulates an ancient shared evolutionary origin with bacterial NhaA. Although plasma membrane H(+) gradients have been observed in some specialized mammalian cells, the ubiquitous tissue distribution of NHA2 suggests that H(+)-coupled transport is more widespread. The coexistence of Na(+) and H(+)-driven chemiosmotic circuits has implications for salt and pH regulation in the kidney.
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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.