ArticleThe Journal of biological chemistry2016
The European Eel NCCβ Gene Encodes a Thiazide-resistant Na-Cl Cotransporter.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Molecular mechanisms of thiazide-like diuretics-mediated inhibition of the human Na-Cl cotransporter.Nature communications · 2025Article
- Structural bases for NaNature communications · 2024Article
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Thirty years of the NaCl cotransporter: from cloning to physiology and structure.American journal of physiology. Renal physiology · 2023Review
- Molecular Physiological Evidence for the Role of NaInternational journal of molecular sciences · 2023Article
- NaPhysiological genomics · 2023Article
- Structure-function relationships in the sodium chloride cotransporter.Frontiers in physiology · 2023Review
- Arterial Blood Pressure, Neuronal Excitability, Mineral Metabolism and Cell Volume Regulation Mechanisms Revealed byMembranes · 2022Article
- The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis.Biomedicines · 2022Review
- The European and Japanese eel NaCl cotransporters β exhibit chloride currents and are resistant to thiazide type diuretics.American journal of physiology. Cell physiology · 2022Article
- Tissue and salinity specific NaScientific reports · 2021Article
- WNK3 and WNK4 exhibit opposite sensitivity with respect to cell volume and intracellular chloride concentration.American journal of physiology. Cell physiology · 2020Article
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The thiazide-sensitive Na-Cl cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian distal convoluted tubule. NCC plays a key role in the regulation of blood pressure. Its inhibition with thiazides constitutes the primary baseline therapy for arterial hypertension. However, the thiazide-binding site in NCC is unknown. Mammals have only one gene encoding for NCC. The eel, however, contains a duplicate gene. NCCα is an ortholog of mammalian NCC and is expressed in the kidney. NCCβ is present in the apical membrane of the rectum. Here we cloned and functionally characterized NCCβ from the European eel. The cRNA encodes a 1043-amino acid membrane protein that, when expressed in Xenopus oocytes, functions as an Na-Cl cotransporter with two major characteristics, making it different from other known NCCs. First, eel NCCβ is resistant to thiazides. Single-point mutagenesis supports that the absence of thiazide inhibition is, at least in part, due to the substitution of a conserved serine for a cysteine at position 379. Second, NCCβ is not activated by low-chloride hypotonic stress, although the unique Ste20-related proline alanine-rich kinase (SPAK) binding site in the amino-terminal domain is conserved. Thus, NCCβ exhibits significant functional differences from NCCs that could be helpful in defining several aspects of the structure-function relationship of this important cotransporter.
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