ArticleThe Journal of physiology2011
Role of an extracellular loop in determining the stoichiometry of Na+-HCO₃⁻ cotransporters.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Review
- pH regulating mechanisms of astrocytes: A critical component in physiology and disease of the brain.Cell calcium · 2024Review
- Potential Theranostic Roles of SLC4 Molecules in Human Diseases.International journal of molecular sciences · 2023Review
- Understanding the Physiological Role of Electroneutral NaPharmaceuticals (Basel, Switzerland) · 2022Review
- Carbonic anhydrases enhance activity of endogenous Na-H exchangers and not the electrogenic Na/HCOThe Journal of physiology · 2020Article
- pH and male fertility: making sense on pH homeodynamics throughout the male reproductive tract.Cellular and molecular life sciences : CMLS · 2019Review
- Structure and Function of SLC4 Family [Formula: see text] Transporters.Frontiers in physiology · 2015Article
- The Role of Flexible Loops in Folding, Trafficking and Activity of Equilibrative Nucleoside Transporters.PloS one · 2015Article
- Cation-coupled bicarbonate transporters.Comprehensive Physiology · 2014Review
- NBCe1 as a model carrier for understanding the structure-function properties of Na⁺ -coupled SLC4 transporters in health and disease.Pflugers Archiv : European journal of physiology · 2014Review
- Article
- Proximal renal tubular acidosis mediated by mutations in NBCe1-A: unraveling the transporter's structure-functional properties.Frontiers in physiology · 2013Review
- Effects of optional structural elements, including two alternative amino termini and a new splicing cassette IV, on the function of the sodium-bicarbonate cotransporter NBCn1 (SLC4A7).The Journal of physiology · 2013Article
- Molecular mechanisms of renal and extrarenal manifestations caused by inactivation of the electrogenic Na(+)-HCO3 (-) cotransporter NBCe1.Frontiers in physiology · 2013Review
- Structure, function, and regulation of the SLC4 NBCe1 transporter and its role in causing proximal renal tubular acidosis.Current opinion in nephrology and hypertension · 2013Review
- Missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis.American journal of physiology. Cell physiology · 2013Article
- The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters.Physiological reviews · 2013Review
- Article
- Effect of simultaneously replacing putative TM6 and TM12 of human NBCe1-A with those from NBCn1 on surface abundance in Xenopus oocytes.The Journal of membrane biology · 2012Article
- PSD-95 interacts with NBCn1 and enhances channel-like activity without affecting Na/HCO(3) cotransport.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2012Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The Na+–HCO₃⁻ cotransporters (NBCs) of the solute carrier 4 family (SLC4) are critical for regulating pH in cells as well as in fluids such as blood and cerebrospinal fluid. Moreover, mutations and gene disruptions in NBC are linked to a wide range of pathologies. NBCe1 (SLC4A4) is electrogenic because it has an apparent Na+:HCO₃⁻ stoichiometry of 1:2 or 1:3, whereas NBCn1 (SLC4A7) is electroneutral because it has an apparent stoichiometry of 1:1. Because stoichiometry influences the effect of transport on membrane potential and vice versa, a central question is what structural features underlie electrogenicity versus electroneutrality. A previous study on rat NBCe1/n1 chimeras demonstrated that the structural elements determining the electrogenicity of NBCe1-A are located within the transmembrane domain, excluding the large third extracellular loop. In the present study we generated a series of chimeras of human NBCe1-A and human NBCn1-A. We found that replacing merely the predicted fourth extracellular loop (EL4) – containing 32 amino acid residues that include 7 prolines – of human NBCe1-A with EL4 of NBCn1-A creates an electroneutral NBC. The opposite switch converts an electroneutral construct to one with electrogenic properties. The introduction of an N-glycosylation site into EL4 confirms that at least a part of it is exposed to the extracellular fluid. We hypothesize that putative EL4 either contributes to the substrate-binding vestibule or indirectly influences substrate binding by interacting with one or more transmembrane segments, thereby controlling the nature of transport.
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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.