Congenital Chloride-losing Diarrhea Causing Mutations in the STAS Domain Result in Misfolding and Mistrafficking of SLC26A3*

@article{Dorwart2008CongenitalCD,
  title={Congenital Chloride-losing Diarrhea Causing Mutations in the STAS Domain Result in Misfolding and Mistrafficking of SLC26A3*},
  author={Michael R. Dorwart and Nikolay Shcheynikov and Jennifer M Baker and Julie Deborah Forman-Kay and Shmuel Muallem and Philip J. Thomas},
  journal={Journal of Biological Chemistry},
  year={2008},
  volume={283},
  pages={8711 - 8722}
}
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-/\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{HCO}_{3}^{-}\) \end{document} exchanger, cause CLD. SLC26A3 is a membrane protein predicted to contain 12 transmembrane-spanning α-helices… 
Update on SLC26A3 mutations in congenital chloride diarrhea
TLDR
None of the studied SLC26A3 mutants shows significant Cl−/HCO  3− exchange activity in vitro, and accordingly, evidence of genotype–phenotype differencies remain nonexistent, and the domain interaction between SLC 26A3 and the cystic fibrosis transmembrane conductance regulator (CFTR) raises a possibility of CFTR modulation in the pathogenesis of CLD.
Effect of SLC26 anion transporter disease-causing mutations on the stability of the homologous STAS domain of E. coli DauA (YchM).
TLDR
It is concluded that the disease-associated mutations destabilized the STAS domain resulting in an increased propensity to misfold and aggregate.
Human MutationMUTATION UPDATE Update on SLC 26 A 3 Mutations in Congenital Chloride Diarrhea
TLDR
None of the studied SLC26A3 mutants shows significant Cl /HCO3 exchange activity in vitro, and accordingly, evidence of genotype–phenotype differencies remain nonexistent, but the domain interaction between SLC 26A3 and the cystic fibrosis transmembrane conductance regulator (CFTR) raises a possibility of CFTR modulation in the pathogenesis of CLD.
Compound Heterozygous Mutations in the SLC26A3 Gene in 2 Spanish Siblings With Congenital Chloride Diarrhea
TLDR
2 novel mutations in 2 siblings with CLD from Andalusia (southern Spain) are described, identified by direct sequencing of the SLC26A3 gene in the child and parents.
Significance of Molecular Testing for Congenital Chloride Diarrhea
TLDR
The diagnosis and therapy of CLD were considerably delayed in 3 of 8 patients from this series, highlighting the potential of misdiagnosing CLD.
A missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR
TLDR
A novel mechanism for human male infertility─impaired anion transport by the coupled SLC26A3 and CFTR is suggested.
Solution Structure of the Guanine Nucleotide-binding STAS Domain of SLC26-related SulP Protein Rv1739c from Mycobacterium tuberculosis*
TLDR
It is demonstrated that Rv1739c STAS binds guanine nucleotides at physiological concentrations and undergoes a ligand-induced conformational change but, unlike anti-σ factor antagonists, may not mediate signals via phosphorylation.
STAS Domain Structure and Function
TLDR
STAS domains are central to membrane targeting of many SulP/SLC26 anion transporters, and STAS domain mutations are associated with at least three human recessive diseases.
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References

SHOWING 1-10 OF 68 REFERENCES
SLC26A7 Is a Cl– Channel Regulated by Intracellular pH*
Members of the SLC26 transporter family play an essential role in several epithelial functions, as revealed by diseases associated with mutations in members of the family. Several members were shown
SLC26A3 mutations in congenital chloride diarrhea
TLDR
A summary of all published and two novel SLC26A3 mutations and polymorphisms are presented, and they are reviewed in the context of their functional consequences and clinical implications.
Mutations of the Down–regulated in adenoma (DRA) gene cause congenital chloride diarrhoea
TLDR
It is concluded that DFIA is an intestinal anion transport molecule that causes chloride diarrhoea when mutated, and is low in undifferentiated (including neoplastic) cells.
Acute regulation of the SLC26A3 congenital chloride diarrhoea anion exchanger (DRA) expressed in Xenopus oocytes
TLDR
Despite the absence of hDRA transcripts in human cell lines derived from CFTR patients, DRA mRNA was present at wild‐type levels in proximal colon and nearly so in the distal ileum of CFTR(‐/‐) mice, suggesting pharmacological modulation of DRA might be a useful adjunct treatment of cystic fibrosis.
Pathogenetics of the human SLC26 transporters.
TLDR
This review article summarizes current information on the pathophysiological consequences of mutations in the human SLC26A2 to A5 genes.
Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes, and diagnostic relevance
Mutations in the DTDST gene can result in a family of skeletal dysplasia conditions which comprise two lethal disorders, achondrogenesis type 1B (ACG1B) and atelosteogenesis type 2 (AO2); and two
The Role of the STAS Domain in the Function and Biogenesis of a Sulfate Transporter as Probed by Random Mutagenesis*
TLDR
The results suggest that the STAS domain is critical for both the activity and biosynthesis/stability of the transporter, and that STAS sub-domains correlate with these specific functions.
Structural and Functional Analysis of the C-terminal STAS (Sulfate Transporter and Anti-sigma Antagonist) Domain of the Arabidopsis thaliana Sulfate Transporter SULTR1.2*
TLDR
Three-dimensional modeling and mutational analyses strengthen the hypothesis that the SULTR1.2 STAS domain is involved in protein-protein interactions that could control sulfate transport.
Genetic background of congenital chloride diarrhea in high-incidence populations: Finland, Poland, and Saudi Arabia and Kuwait.
TLDR
It is confirmed that the same locus is mutated in all cases of CLD studied so far, and in Poland, a relatively common founder mutation is likely to highlight a set of rare mutations that would very rarely produce homozygosity alone, suggesting that mutations in the CLD locus are not rare events.
Cloning and characterization of SLC26A6, a novel member of the solute carrier 26 gene family.
TLDR
The genomic structure of the SLC26A6 gene was determined and excluded mutations in the 21 coding exons as the cause of DFNB6 and USH2B, which closely map to the S LC26A 6 chromosomal locus (3p21).
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