ArticleThe Journal of biological chemistry2008
Congenital chloride-losing diarrhea causing mutations in the STAS domain result in misfolding and mistrafficking of SLC26A3.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Trio-WES and functional validation reveals a novel splice site variant of SLC26A3 in a case with congenital chloride diarrhea and a systematic review of SLC26A3 mutations in China.Molecular genetics and genomics : MGG · 2025Pooled it
- The ZBTB16/CUL3/ROC1 ubiquitin ligase drives the degradation of pathogenic pendrin (SLC26A4) protein variants.Journal of biomedical science · 2026Article
- Solute Carrier Family 26 Member 4 (SLC26A4), A Potential Therapeutic Target for Asthma.Journal of respiratory biology and translational medicine · 2024Article
- SLC26A3/NHERF2-IκB/NFκB/p65 feedback loop suppresses tumorigenesis and metastasis in colorectal cancer.Oncogenesis · 2023Article
- Assistance for Folding of Disease-Causing Plasma Membrane Proteins.Biomolecules · 2020Review
- Structural mechanism of the active bicarbonate transporter from cyanobacteria.Nature plants · 2019Article
- Article
- Importance of SLC26 Transmembrane Anion Exchangers in Sperm Post-testicular Maturation and Fertilization Potential.Frontiers in cell and developmental biology · 2019Review
- Functional characterization of SLC26A3 c.392C>G (p.P131R) mutation in intestinal barrier function using CRISPR/CAS9-created cell models.Cell & bioscience · 2019Article
- Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7.Communications biology · 2019Article
- A missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR.Scientific reports · 2017Article
- Human SLC26A4/Pendrin STAS domain is a nucleotide-binding protein: Refolding and characterization for structural studies.Biochemistry and biophysics reports · 2016Article
- Bicarbonate exchangers SLC26A3 and SLC26A6 are localized at the apical membrane of porcine vas deferens epithelium.Physiological reports · 2015Article
- Functional regulation of the SLC26-family protein prestin by calcium/calmodulin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Regulation of ABCC6 trafficking and stability by a conserved C-terminal PDZ-like sequence.PloS one · 2014Article
- Altered expression and localization of ion transporters contribute to diarrhea in mice with Salmonella-induced enteritis.Gastroenterology · 2013Article
- CFTR-SLC26 transporter interactions in epithelia.Biophysical reviews · 2012Article
- Physiology of epithelial chloride and fluid secretion.Cold Spring Harbor perspectives in medicine · 2012Article
- Guanine nucleotides differentially modulate backbone dynamics of the STAS domain of the SulP/SLC26 transport protein Rv1739c of Mycobacterium tuberculosis.The FEBS journal · 2012Article
- Recent progress in congenital diarrheal disorders.Current gastroenterology reports · 2011Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Congenital chloride-losing diarrhea (CLD) is a genetic disorder causing watery stool and dehydration. Mutations in SLC26A3 (solute carrier 26 family member 3), which functions as a coupled Cl(-)/HCO(3)(-) exchanger, cause CLD. SLC26A3 is a membrane protein predicted to contain 12 transmembrane-spanning alpha-helices and a C-terminal STAS (sulfate transporters and anti-sigma-factor) domain homologous to the bacterial anti-sigma-factor antagonists. The STAS domain is required for SLC26A3 Cl(-)/HCO(3)(-) exchange function and for the activation of cystic fibrosis transmembrane conductance regulator by SLC26A3. Here we investigate the molecular mechanism(s) by which four CLD-causing mutations (DeltaY526/7, I544N, I675/6ins, and G702Tins) in the STAS domain lead to disease. In a heterologous mammalian expression system biochemical, immunohistochemical, and ion transport experiments suggest that the four CLD mutations cause SLC26A3 transporter misfolding and/or mistrafficking. Expression studies with the isolated STAS domain suggest that the I675/6ins and G702Tins mutations disrupt the STAS domain directly, whereas limited proteolysis experiments suggest that the DeltaY526/7 and I544N mutations affect a later step in the folding and/or trafficking pathway. The data suggest that these CLD-causing mutations cause disease by at least two distinct molecular mechanisms, both ultimately leading to loss of functional protein at the plasma membrane.
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