Functional Comparison of Mouse slc26a6 Anion Exchanger with Human SLC26A6 Polypeptide Variants

Chernova, Marina N.; Jiang, Liang; Friedman, David J.; Darman, Rachel; Lohi, Hannes; Kere, Juha; Vandorpe, David H.; Alper, Seth L.

doi:10.1074/jbc.m411703200

Cited by 144 publications

(231 citation statements)

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“…4A). Guinea pig and mouse Slc26a6 exhibited similar rates of Cl Ϫ uptake at pH 7.4, whereas human SLC26A6 mediated much lower Cl Ϫ transport rates as shown previously (7). Robust, H 2 -DIDS-sensitive, substrate concentration-dependent sulfate uptake by gpSlc26a6 was comparable to that measured in oocytes expressing mouse C292 SLC26 ANION EXCHANGERS OF GUINEA PIG PANCREATIC DUCT Slc26a6 (Fig.…”

Section: Molecular Cloning Of Slc26a3 Slc26a6 and Slc26a11 Cdnas Frsupporting

confidence: 83%

“…The H 2 -DIDS-sensitive and -insensitive components of apical membrane Cl Ϫ /HCO 3 Ϫ exchange in isolated interlobular ducts from guinea pig pancreas (53) may correspond, respectively, to Slc26a6 and Slc26a3 (7,8,53). Slc26a11 was also detected in guinea pig pancreas.…”

Section: Discussionmentioning

confidence: 99%

“…Anion exchange activities of human SLC26A3, SLC26A6, and SLC26A11 differ in their sensitivities to inhibition by stilbene disulfonates (7,8,57). The isolated guinea pig pancreatic interlobular duct exhibits both H 2 -DIDS-sensitive and H 2 -DIDS-insensitive components of apical Cl Ϫ / HCO 3 Ϫ exchange (53).…”

Section: A-c)mentioning

confidence: 99%

“…Other plausible candidate Slc26-regulatory cofactors include carbonic anhydrases (2), inositol-1,4,5-trisphosphate (IP3) receptor-binding protein released with IP3 (IRBIT) (61), and with-no-lysine (WNK) kinases (35). Functional studies of chimeric inter-ortholog domain-swap constructs (7,9) could identify the Slc26a6 sequence or subdomain interacting with the hypothetical cofactor in a species-specific and/or host expression cell-specific manner.…”

Section: C297mentioning

confidence: 99%

“…These results prompted us to clone cDNAs encoding Slc26a3, Slc26a6, and Slc26a11 polypeptides from the guinea pig and to compare their functional characteristics in Xenopus oocytes with those of their mouse and human orthologs (7)(8)(9)57), as well as with apical Cl Ϫ /HCO 3 Ϫ exchange of isolated, perfused guinea pig pancreatic interlobular ducts (53).…”

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confidence: 99%

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SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization

Stewart

Shmukler

Vandorpe

et al. 2011

American Journal of Physiology-Cell Physiology

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The secretin-stimulated human pancreatic duct secretes HCO3−-rich fluid essential for normal digestion. Optimal stimulation of pancreatic HCO3− secretion likely requires coupled activities of the cystic fibrosis transmembrane regulator (CFTR) anion channel and apical SLC26 Cl−/HCO3− exchangers. However, whereas stimulated human and guinea pig pancreatic ducts secrete ∼140 mM HCO3− or more, mouse and rat ducts secrete ∼40–70 mM HCO3−. Moreover, the axial distribution and physiological roles of SLC26 anion exchangers in pancreatic duct secretory processes remain controversial and may vary among mammalian species. Thus the property of high HCO3− secretion shared by human and guinea pig pancreatic ducts prompted us to clone from guinea pig pancreatic duct cDNAs encoding Slc26a3, Slc26a6, and Slc26a11 polypeptides. We then functionally characterized these anion transporters in Xenopus oocytes and human embryonic kidney (HEK) 293 cells. In Xenopus oocytes, gpSlc26a3 mediated only Cl−/Cl− exchange and electroneutral Cl−/HCO3− exchange. gpSlc26a6 in Xenopus oocytes mediated Cl−/Cl− exchange and bidirectional exchange of Cl− for oxalate and sulfate, but Cl−/HCO3− exchange was detected only in HEK 293 cells. gpSlc26a11 in Xenopus oocytes exhibited pH-dependent Cl−, oxalate, and sulfate transport but no detectable Cl−/HCO3− exchange. The three gpSlc26 anion transporters exhibited distinct pharmacological profiles of 36Cl− influx, including partial sensitivity to CFTR inhibitors Inh-172 and GlyH101, but only Slc26a11 was inhibited by PPQ-102. This first molecular and functional assessment of recombinant SLC26 anion transporters from guinea pig pancreatic duct enhances our understanding of pancreatic HCO3− secretion in species that share a high HCO3− secretory output.

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Section: Molecular Cloning Of Slc26a3 Slc26a6 and Slc26a11 Cdnas Frsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: A-c)mentioning

confidence: 99%

Section: C297mentioning

confidence: 99%

mentioning

confidence: 99%

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SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization

Stewart

Shmukler

Vandorpe

et al. 2011

American Journal of Physiology-Cell Physiology

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Age‐dependent transcriptional and epigenomic responses to light exposure in the honey bee brain

et al. 2016

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Light is a powerful environmental stimulus of special importance in social honey bees that undergo a behavioral transition from in‐hive to outdoor foraging duties. Our previous work has shown that light exposure induces structural neuronal plasticity in the mushroom bodies ( MB s), a brain center implicated in processing inputs from sensory modalities. Here, we extended these analyses to the molecular level to unravel light‐induced transcriptomic and epigenomic changes in the honey bee brain. We have compared gene expression in brain compartments of 1‐ and 7‐day‐old light‐exposed honey bees with age‐matched dark‐kept individuals. We have found a number of differentially expressed genes ( DEG s), both novel and conserved, including several genes with reported roles in neuronal plasticity. Most of the DEG s show age‐related changes in the amplitude of light‐induced expression and are likely to be both developmentally and environmentally regulated. Some of the DEG s are either known to be methylated or are implicated in epigenetic processes suggesting that responses to light exposure are at least partly regulated at the epigenome level. Consistent with this idea light alters the DNA methylation pattern of bgm , one of the DEG s affected by light exposure, and the expression of micro RNA miR‐932 . This confirms the usefulness of our approach to identify candidate genes for neuronal plasticity and provides evidence for the role of epigenetic processes in driving the molecular responses to visual stimulation.

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Molecular Mechanisms and Regulation of Urinary Acidification

Kurtz

2014

Comprehensive Physiology

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The H+ concentration in human blood is kept within very narrow limits, ~ 40 nM, despite the fact that dietary metabolism generates acid and base loads that are added to the systemic circulation throughout the life of mammals. One of the primary functions of the kidney is to maintain the constancy of systemic acid-base chemistry. The kidney has evolved the capacity to regulate blood acidity by performing three key functions: 1) reabsorb HCO3− that is filtered through the glomeruli to prevent its excretion in the urine; 2) generate a sufficient quantity of new HCO3− to compensate for the loss of HCO3− resulting from dietary metabolic H+ loads and loss of HCO3− in the urea cycle; and 3) excrete HCO3− (or metabolizable organic anions) following a systemic base load. The ability of the kidney to perform these functions requires that various cell types throughout the nephron respond to changes in acid-base chemistry by modulating specific ion transport and/or metabolic processes in a coordinated fashion such that the urine and renal vein chemistry is altered appropriately. The purpose of the article is to provide the interested reader with a broad review of a field that began historically ~ 60 years ago with whole animal studies, and has evolved to where we are currently addressing questions related to kidney acid-base regulation at the single protein structure/function level.

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Functional Comparison of Mouse slc26a6 Anion Exchanger with Human SLC26A6 Polypeptide Variants

Abstract: The unusually low 78% amino acid identity between the orthologous human SLC26A6 and mouse slc26a6 polypeptides prompted systematic comparison of their anion transport functions in Xenopus oocytes. Multiple human SLC26A6 variant polypeptides were also functionally compared.

Cited by 144 publications

References 60 publications

SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization

SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization

Age‐dependent transcriptional and epigenomic responses to light exposure in the honey bee brain

Molecular Mechanisms and Regulation of Urinary Acidification

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