ArticleAmerican journal of physiology. Cell physiology2013
Missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 35 citations in OpenAlex.
- Functional Characterization of a Novel SLC4A4 Variant and Uniparental Isodisomy in Proximal Renal Tubular Acidosis Patient.Biochemical genetics · 2024Article
- On the substrate turnover rate of NBCe1 and AE1 SLC4 transporters: structure-function considerations.Frontiers in physiology · 2024Article
- Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney.International journal of molecular sciences · 2023Review
- Lack of Charge Interaction in the Ion Binding Site Determines Anion Selectivity in the Sodium Bicarbonate Cotransporter NBCe1.International journal of molecular sciences · 2022Article
- Revisiting the Role of Ser982 Phosphorylation in Stoichiometry Shift of the Electrogenic NaInternational journal of molecular sciences · 2021Article
- Carboxyl Ester Lipase May Not Mediate Lipotoxic Injury during Severe Acute Pancreatitis.The American journal of pathology · 2019Article
- Renal Tubular Acidosis: HAdvances in chronic kidney disease · 2018Review
- Mouse models of SLC4-linked disorders of HCOAmerican journal of physiology. Cell physiology · 2018Review
- CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1.Nature communications · 2018Article
- Ammonia Transporters and Their Role in Acid-Base Balance.Physiological reviews · 2017Review
- A novel mutant NaThe Journal of physiology · 2016Article
- NBCe1 expression is required for normal renal ammonia metabolism.American journal of physiology. Renal physiology · 2015Article
- TASK-2 K₂p K⁺ channel: thoughts about gating and its fitness to physiological function.Pflugers Archiv : European journal of physiology · 2015Review
- Interplay between disulfide bonding and N-glycosylation defines SLC4 Na+-coupled transporter extracellular topography.The Journal of biological chemistry · 2015Article
- Regulators of Slc4 bicarbonate transporter activity.Frontiers in physiology · 2015Review
- Molecular mechanisms and regulation of urinary acidification.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
- Facilitation by intracellular carbonic anhydrase of Na+ -HCO3- co-transport but not Na+ / H+ exchange activity in the mammalian ventricular myocyte.The Journal of physiology · 2014Article
- A novel delta current method for transport stoichiometry estimation.BMC biophysics · 2014Article
- Proximal renal tubular acidosis mediated by mutations in NBCe1-A: unraveling the transporter's structure-functional properties.Frontiers in physiology · 2013Review
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8 authors at 2 institutions in 1 country.
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Abstract
Mutations in SLC4A4, the gene encoding the electrogenic Na(+)-HCO3(-) cotransporter NBCe1, cause severe proximal renal tubular acidosis (pRTA), growth retardation, decreased IQ, and eye and teeth abnormalities. Among the known NBCe1 mutations, the disease-causing mechanism of the T485S (NBCe1-A numbering) mutation is intriguing because the substituted amino acid, serine, is structurally and chemically similar to threonine. In this study, we performed intracellular pH and whole cell patch-clamp measurements to investigate the base transport and electrogenic properties of NBCe1-A-T485S in mammalian HEK 293 cells. Our results demonstrated that Ser substitution of Thr485 decreased base transport by ~50%, and importantly, converted NBCe1-A from an electrogenic to an electroneutral transporter. Aqueous accessibility analysis using sulfhydryl reactive reagents indicated that Thr485 likely resides in an NBCe1-A ion interaction site. This critical location is also supported by the finding that G486R (a pRTA causing mutation) alters the position of Thr485 in NBCe1-A thereby impairing its transport function. By using NO3(-) as a surrogate ion for CO3(2-), our result indicated that NBCe1-A mediates electrogenic Na(+)-CO3(2-) cotransport when functioning with a 1:2 charge transport stoichiometry. In contrast, electroneutral NBCe1-T485S is unable to transport NO3(-), compatible with the hypothesis that it mediates Na(+)-HCO3(-) cotransport. In patients, NBCe1-A-T485S is predicted to transport Na(+)-HCO3(-) in the reverse direction from blood into proximal tubule cells thereby impairing transepithelial HCO3(-) absorption, possibly representing a new pathogenic mechanism for generating human pRTA.
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