Disease relevance of SLC26A6

• Our results support the general concept of microdomain organization for ion transport and suggest a mechanism for cystic fibrosis transmembrane regulator (CFTR)-mediated SLC26A6 upregulation in pancreatic duct cells [1].

High impact information on SLC26A6

• We report here a reciprocal regulatory interaction between the SLC26T DRA, SLC26A6 and CFTR [2].
• Involvement of the anion exchanger SLC26A6 in prostaglandin E2- but not forskolin-stimulated duodenal HCO3- secretion [3].
• The present study was designed to examine the role of SLC26A6 in prostaglandin E(2) (PGE(2))-, forskolin-, and carbachol-induced duodenal HCO(3)(-) secretion [3].
• RESULTS: Basal HCO(3)(-) secretion was diminished by 20%, PGE(2)-stimulated HCO(3)(-) secretory response by 59%, and carbachol-stimulated response was reduced by 35% in SLC26A6-/- compared with +/+ duodenal mucosa, whereas the forskolin-stimulated HCO(3)(-) secretory response was not different [3].
• METHODS: Murine duodenal mucosal HCO(3)(-) secretion was examined in vitro in Ussing chambers and mucosal SLC26A6 expression levels were analyzed by semiquantitative reverse-transcription polymerase chain reaction [3].

Biological context of SLC26A6

• Role of anion exchange transporter PAT1 (SLC26A6) in intestinal absorption of organic anions [4].

Anatomical context of SLC26A6

• Expression in MDCK cells and in Xenopus oocytes demonstrated trafficking of the SLC26A6 protein to the cell membrane but did not reveal anion transport activity with tracer uptake or intracellular pH measurements [5].
• Northern blot analysis showed the highest SLC26A6 transcript levels in kidney and pancreas [5].
• Pancreatic ductal cell lines Capan-1 and Capan-2 express SLC26A6, and immunohistochemistry localizes SLC26A6 protein to the apical surface of pancreatic ductal cells, suggesting it as a candidate for a luminal anion exchanger [6].
• The functional versatility of SLC26A6 identifies it as the primary candidate for the apical Cl(-)-formate/oxalate and Cl(-)-base exchanger of brush border membranes in the renal proximal tubule, with a central role in the reabsorption of Na(+)-Cl(-) from the glomerular ultrafiltrate [7].
• This review in particular focuses on the role and regulation of SLC26A6, A7 and A9 in the kidney and/or gastrointestinal tract [8].

Associations of SLC26A6 with chemical compounds

• At least three of the SLC26 exchangers mediate electrogenic Cl(-)-HCO(3)(-) and Cl(-)-OH(-) exchange; the stoichiometry of Cl(-)-HCO(3)(-) exchange appears to differ between SLC26 paralogs, such that SLC26A3 transports >/=2 Cl(-) ions per HCO(3)(-) ion, whereas SLC26A6 transports >/=2 HCO(3)(-) ions per Cl(-) ion [7].
• BACKGROUND: The anion transporters SLC26A6 (PAT1) and SLC26A7, transporting at least chloride, oxalate, sulfate and bicarbonate, show a distinct expression and function in different mammalian species [9].
• Differential regulation of Cl--base exchange mediated by SLC26A6, and Na+-H+ exchange mediated by NHE3, may act as a switch to govern the ratio of transcellular NaHCO3 to NaCl reabsorption in the proximal tubule [10].
• Angiotensin II (AngII), which activates PKC, decreased Cl-/HCO3- exchange in cells coexpressing SLC26A6 and AT1a-AngII receptor [11].
• Immunofluorescence studies on transiently transfected cells indicated membrane localization and indicated that both NH(2)- and COOH-terminal tails of the SLC26A6 variants are located intracellularly, suggesting a topology with an even number of transmembrane domains [1].

Other interactions of SLC26A6

• SLC26A6 and SLC26A7 anion exchangers have a distinct distribution in human kidney [9].
• In contrast, SLC26A6 (CFEX, PAT1) is expressed on the brush border of proximal tubule cells [10].
• Cl(-)-HCO(3)(-) and Cl(-)-OH(-) exchange activity of SLC26A6 and AE3 were investigated in transfected HEK293 cells, using intracellular fluorescence measurements of 2',7'-bis (2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF), to monitor intracellular pH (pH(i)) [12].
• Finally, we demonstrated an essential role for the scaffolding protein PDZK1 in apical membrane expression of SLC26A6 [13].
• By a genome-driven approach, several new SLC26 family members have been identified, including a kidney- and pancreas-specific gene, SLC26A6 [1].

Analytical, diagnostic and therapeutic context of SLC26A6

• In this study we used a homology approach combined with RACE PCR to identify human SLC26A6, the sixth member of this gene family [5].

References