ArticlePflugers Archiv : European journal of physiology2013
Identification of dominant negative effect of L522P mutation in the electrogenic Na⁺-HCO₃⁻ cotransporter NBCe1.
Article in Pflugers Archiv : European journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- The role of NaPflugers Archiv : European journal of physiology · 2024Review
- Understanding the Functional Expression of Na+-Coupled SLC4 Transporters in the Renal and Nervous Systems: A Review.Brain sciences · 2021Review
- SLC4A4 compound heterozygous mutations in exon-intron boundary regions presenting with severe proximal renal tubular acidosis and extrarenal symptoms coexisting with Turner's syndrome: a case report.BMC medical genetics · 2018Article
- A pure chloride channel mutant of CLC-5 causes Dent's disease via insufficient V-ATPase activation.Pflugers Archiv : European journal of physiology · 2016Article
- 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
- Proximal renal tubular acidosis mediated by mutations in NBCe1-A: unraveling the transporter's structure-functional properties.Frontiers in physiology · 2013Review
- 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
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9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homozygous mutations in the electrogenic Na(+)-HCO3 (-) cotransporter NBCe1 cause proximal renal tubular acidosis (pRTA) associated with extrarenal manifestations such as ocular abnormalities and migraine. Previously, the NBCe1 cytosolic mutant S982NfsX4 was shown to have a dominant negative effect by forming hetero-oligomer complexes with wild type (WT), which might be responsible for the occurrence of glaucoma and migraine in the heterozygous family members. In this study, we investigated whether the NBCe1 L522P mutant has a similar dominant negative effect. Functional analyses in Xenopus oocytes and HEK293 cells revealed that the L522P mutant had no transport activity due to defective membrane expression. Furthermore, when coexpressed with WT, L522P significantly reduced the transport activity of WT. In HEK293 cells, the cytosolic mutant L522P reduced the membrane expression of NBCe1 by forming hetero-oligomer complexes with WT. Among the artificial Leu(522) mutants, L522I showed proper membrane expression and normal transport activity. However, the other mutants L522R, L522K, L522D, and L522E showed a predominant cytosolic retention. Moreover, L522R had a dominant negative effect, when coexpressed with WT. These results indicate that Leu(522) plays an important role in the structure and trafficking of NBCe1. They also suggest that the NBCe1 mutants retaining in cytoplasm may have the dominant negative effect in common, which may induce some clinical manifestations.
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