Slc26a9—Anion Exchanger, Channel and Na+ Transporter

Chang, Min; Plata, Consuelo; Zandi‐Nejad, Kambiz; Sinđić, Aleksandra; Sussman, Caroline R.; Mercado, Adriana; Broumand, Vadjista; Raghuram, Viswanathan; Mount, David B.; Romero, Michael F.

doi:10.1007/s00232-009-9165-5

Cited by 83 publications

(104 citation statements)

References 60 publications

(111 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3 shows two experiments measuring intracellular pH (pH i ) in the presence of CO 2 /HCO 3 Ϫ . As we have shown previously for Slc26a9 (10), removal of Cl Ϫ in CO 2 /HCO 3 Ϫ results in an alkalinization (1pH i ) and depolarization (Fig. 3A), i.e.…”

Section: B Lane 10 C Lane 10)supporting

confidence: 83%

“…Cloning and characterization of Slc26a9 was recently reported by our group (10). All of the Slc26a9 constructs used for functional expression were subcloned into the X. laevis expression vector pGEMHE.…”

Section: Slc26a9 Constructsmentioning

confidence: 99%

“…Electrophysiology protocols were performed as previously reported for Slc26a9 (10). All solutions were either ND96 (96 mM NaCl, 2 mM KCl, 1.8 mM CaCl 2 , 1 mM MgCl 2 , 5 mM HEPES, pH 7.5) or iso-osmotic ion replacements (23).…”

Section: Electrophysiologymentioning

confidence: 99%

“…Loriol and co-workers (12) indicated that SLC26A9 has a Cl Ϫ conductance that may be stimulated by HCO 3 Ϫ . Two other groups have indicated that the Cl Ϫ conductance is not affected by the presence of HCO 3 Ϫ (10,11). We have recently demonstrated that Slc26a9 functions as both an electrogenic nCl Ϫ -HCO 3 Ϫ exchanger and a Cl Ϫ channel (10).…”

mentioning

confidence: 99%

“…Slc26a9 protein has been localized to epithelia of the stomach and lung (9,10,14), although mRNA is also detectable in brain, heart, kidney, small intestine, thymus, and ovary (10). The R-region of CFTR was previously shown to increase the activity of Slc26a3 and Slc26a6 by interaction with STAS domains (6,15,16).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Slc26a9 Is Inhibited by the R-region of the Cystic Fibrosis Transmembrane Conductance Regulator via the STAS Domain

Chang

Plata

Sinđić

et al. 2009

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

SLC26 proteins function as anion exchangers, channels, and sensors. Previous cellular studies have shown that Slc26a3 and Slc26a6 interact with the R-region of the cystic fibrosis transmembrane conductance regulator (CFTR), (R)CFTR, via theSlc26 genes and proteins have attracted the attention of physiologists and geneticists. Why? Slc26a1 (Sat-1) was characterized as a Na ϩ -independent SO 4 2Ϫ transporter (1). Given the transport characteristics of the founding member of the gene family, Slc26 proteins were assumed to be sulfate transporters. Disease phenotypes, clone characterization, and family additions demonstrate that the Slc26 proteins are anion transporters or channels (2-4). These proteins have varied tissue expression patterns. At one extreme, Slc26a5 in mammals is found in the hair cells of the inner ear (5), whereas Slc26a2 (DTDST) is virtually ubiquitous in epithelial tissues (2).Several Slc26 proteins are found in the epithelia of the lung, intestine, stomach, pancreas, and kidney, usually in apical membranes. Interestingly these are also tissues and membranes in which the cystic fibrosis transmembrane conductance regulator (CFTR) 5 has been found functionally or by immunohistochemistry. Ko and co-workers (6 -8) examined the distribution of Slc26a3 and Slc26a6 in HCO 3 Ϫ secretory epithelia, and asked if an interaction might occur between these Slc26 proteins and CFTR. In particular, these studies indicate that in expression systems, there is a reciprocal-stimulatory interaction of the STAS (sulfate transporter anti-sigma) domains of Slc26a3 and Slc26a6 with the regulatory region (R-region) of CFTR. These investigators hypothesized that this stimulatory interaction could account for the differences in pancreatic insufficiency and sufficiency observed in cystic fibrosis patients. Nevertheless, knock-out Slc26a6 mouse studies reveal more complicated cell and tissue physiology (see "Discussion").Slc26a9 has been reported to be a Cl Ϫ -HCO 3 Ϫ exchanger (9, 10) or a large Cl Ϫ conductance (3,11,12). Loriol and co-workers (12) indicated that SLC26A9 has a Cl Ϫ conductance that may be stimulated by HCO 3 Ϫ . Two other groups have indicated that the Cl Ϫ conductance is not affected by the presence of HCO 3 Ϫ (10, 11). We have recently demonstrated that Slc26a9 functions as both an electrogenic nCl Ϫ -HCO 3 Ϫ exchanger and a Cl Ϫ channel (10). Dorwart and colleagues (11) found that WNK kinases inhibited the SLC26A9 Cl Ϫ conductance but that this effect was independent of kinase activity. One group has a preliminary report indicating that WNK3 decreased Cl Ϫ uptake,

show abstract

Section: B Lane 10 C Lane 10)supporting

confidence: 83%

Section: Slc26a9 Constructsmentioning

confidence: 99%

Section: Electrophysiologymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Slc26a9 Is Inhibited by the R-region of the Cystic Fibrosis Transmembrane Conductance Regulator via the STAS Domain

Chang

Plata

Sinđić

et al. 2009

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

Slc26 Family of Anion Transporters in the Gastrointestinal Tract: Expression, Function, Regulation, and Role in Disease

Seidler

Nikolovska

2019

Comprehensive Physiology

View full text Add to dashboard Cite

SLC26 family members are multifunctional transporters of small anions, including Cl − , HCO 3 − , sulfate, oxalate, and formate. Most SLC26 isoforms act as secondary (coupled) anion transporters, while others mediate uncoupled electrogenic transport resembling Cl − channels. Of the 11 described SLC26 isoforms, the SLC26A1,2,3,6,7,9,11 are expressed in the gastrointestinal tract, where they participate in salt and water transport, surface pH‐microclimate regulation, affect the microbiome composition, the absorption, and secretion of oxalate and sulfate, and other functions that require further study. Several intestinal or extra‐intestinal diseases are related to SLC26A mutations. Patients with congenital chloride diarrhea (CLD) suffer from Cl − ‐rich acidic diarrhea and systemic alkalosis due to SLC26A3 mutations. Patients with osteochondrodysplastic syndromes experience skeletal defects due to SLC26A2 mutations, resulting in defective sulfate absorption in enterocytes and sulfate uptake in chondrocytes. Because of functional interactions between SLC26 and other proteins, such as the Cl − channel CFTR, some of the intestinal cystic fibrosis manifestations may be attributed to impaired SLC26 isoform localization and function. The altered expression of SLC26 members due to inflammation or operative procedures have important consequences on intestinal transport and barrier function in common diseases as inflammatory bowel disease or bariatric surgery. The present review gives an overview on the current state of knowledge of the intestinally expressed SLC26A isoforms (SLC26A1,2,3,6,7,9,11) from the history of their functional identification, cloning and expression, the insights into their function, interaction partners and regulation gained in heterologous expression systems and Slc26a‐deficient mice, to information about their transcriptional regulation and roles in gastrointestinal disease manifestations. © 2019 American Physiological Society. Compr Physiol 9:839‐872, 2019.

show abstract

Oxalate Flux Across the Intestine: Contributions from Membrane Transporters

Whittamore

Hatch

2021

Comprehensive Physiology

View full text Add to dashboard Cite

Slc26a9—Anion Exchanger, Channel and Na+ Transporter

Cited by 83 publications

References 60 publications

Slc26a9 Is Inhibited by the R-region of the Cystic Fibrosis Transmembrane Conductance Regulator via the STAS Domain

Slc26a9 Is Inhibited by the R-region of the Cystic Fibrosis Transmembrane Conductance Regulator via the STAS Domain

Slc26 Family of Anion Transporters in the Gastrointestinal Tract: Expression, Function, Regulation, and Role in Disease

Oxalate Flux Across the Intestine: Contributions from Membrane Transporters

Contact Info

Product

Resources

About