Structure, Function, and Trafficking of SLC4 and SLC26 Anion Transporters

Cordat, Emmanuelle; Reithmeier, Reinhart A.F.

doi:10.1016/b978-0-12-800223-0.00001-3

Cited by 53 publications

(37 citation statements)

References 349 publications

(330 reference statements)

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“…13). Consequently, it participates in the regulation of the intracellular pH, ion and volume homeostasis of the erythrocyte14 and in acid secretion in the kidney.…”

mentioning

confidence: 99%

Stomatin modulates the activity of the Anion Exchanger 1 (AE1, SLC4A1)

Genetet

Desrames

Chouali

et al. 2017

Sci Rep

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Anion Exchanger 1 (AE1) and stomatin are integral proteins of the red blood cell (RBC) membrane. Erythroid and kidney AE1 play a major role in HCO3− and Cl− exchange. Stomatins down-regulate the activity of many channels and transporters. Biochemical studies suggested an interaction of erythroid AE1 with stomatin. Moreover, we previously reported normal AE1 expression level in stomatin-deficient RBCs. Here, the ability of stomatin to modulate AE1-dependent Cl−/HCO3− exchange was evaluated using stopped-flow methods. In HEK293 cells expressing recombinant AE1 and stomatin, the permeabilities associated with AE1 activity were 30% higher in cells overexpressing stomatin, compared to cells with only endogenous stomatin expression. Ghosts from stomatin-deficient RBCs and controls were resealed in the presence of pH- or chloride-sensitive fluorescent probes and submitted to inward HCO3− and outward Cl− gradients. From alkalinization rate constants, we deduced a 47% decreased permeability to HCO3− for stomatin-deficient patients. Similarly, kinetics of Cl− efflux, followed by the probe dequenching, revealed a significant 42% decrease in patients. In situ Proximity Ligation Assays confirmed an interaction of AE1 with stomatin, in both HEK recombinant cells and RBCs. Here we show that stomatin modulates the transport activity of AE1 through a direct protein-protein interaction.

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“…13). Consequently, it participates in the regulation of the intracellular pH, ion and volume homeostasis of the erythrocyte14 and in acid secretion in the kidney.…”

mentioning

confidence: 99%

Stomatin modulates the activity of the Anion Exchanger 1 (AE1, SLC4A1)

Genetet

Desrames

Chouali

et al. 2017

Sci Rep

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“…The electrogenic Na ϩ -HCO 3 Ϫ cotransporter (NBCe2, also referred as NBC4) is encoded by the SLC4A5 gene. It is notable that members of the SLC4 family, as recently reviewed (9,10,32,34), are involved in dRTA. Recent studies have suggested that NBCe2 expresses in the distal nephron and is involved in acid/base regulation in the renal distal tubule (11,15).…”

mentioning

confidence: 99%

Deficient acid handling with distal RTA in the NBCe2 knockout mouse

Wen

Yuan

Cornelius

et al. 2015

American Journal of Physiology-Renal Physiology

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In the present study, we report that a mouse model lacking the electrogenic Na ϩ -HCO 3 Ϫ cotransporter [NBCe2/Slc4a5; NBCe2 knockout (KO) mice] developed dRTA after an oral acid challenge. NBCe2 expression was identified in the connecting tubule (CNT) of wild-type mice, and its expression was significantly increased after acid loading. NBCe2 KO mice did not have dRTA when on a standard mouse diet. However, after acid loading, NBCe2 KO mice exhibited complete features of dRTA, characterized by insufficient urinary acidification, hyperchloremic hypokalemic metabolic acidosis, and hypercalciuria. Additional experiments showed that NBCe2 KO mice had decreased luminal transepithelial potential in the CNT, as revealed by micropuncture. Further immunofluorescence and Western blot experiments found that NBCe2 KO mice had increased expression of H ϩ -ATPase B1 in the plasma membrane. These results showed that NBCe2 KO mice with acid loading developed increased urinary K ϩ and Ca 2ϩ wasting due to decreased luminal transepithelial potential in the CNT. NBCe2 KO mice compensated to maintain systemic pH by increasing H ϩ -ATPase in the plasma membrane.

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“…The highly conserved human SLC26 gene family includes 11 members encoding at least 10 polypeptide gene products that mediate electroneutral or electrogenic anion transport in many cell and tissue types [15]. The SLC26 proteins are N-glycosylated [44] homodimers [14] (or tetramers [5,78]) with short N-terminal cytoplasmic domains followed by 14 transmembrane spans and C-terminal cytoplasmic STAS domains of variable length [3,24].…”

Section: Introductionmentioning

confidence: 99%

“…The SLC26 proteins are N-glycosylated [44] homodimers [14] (or tetramers [5,78]) with short N-terminal cytoplasmic domains followed by 14 transmembrane spans and C-terminal cytoplasmic STAS domains of variable length [3,24]. Mammalian SLC26 proteins transport small anion substrates including Cl − , HCO 3 − , OH − , SO 4 2− , oxalate, I − , and formate [56], whereas SLC26-related SulP proteins transport dicarboxylates, as well [36,74], playing important roles in maintaining cellular anion homeostasis [15]. Human SLC26 mutations cause Mendelian diseases such as diastrophic (chondro)dysplasia ( SLC26A2 ) [4], congenital chloride diarrhea ( SLC26A3 ) [80], Pendred syndrome or isolated enlargement of the vestibular acqueduct ( SLC26A4 ) [8,79], and impaired male fertility ( SLC26A8) [21].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Cl− regulates human SO4 2−/anion exchanger SLC26A1 by altering pH sensitivity of anion transport

Heneghan

Vandorpe

et al. 2016

Pflugers Arch - Eur J Physiol

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Genetic deficiency of the SLC26A1 anion exchanger in mice is known to be associated with hyposulfatemia and hyperoxaluria with nephrolithiasis, but many aspects of human SLC26A1 function remain to be explored. We report here the functional characterization of human SLC26A1, a DIDS-sensitive, electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, bicarbonate, thiosulfate and (with divergent properties) chloride. Human SLC26A1-mediated anion exchange differs from that of its rodent orthologs in its stimulation by alkaline pHo and inhibition by acidic pHo but not pHi, and in its failure to transport glyoxylate. SLC26A1-mediated transport of sulfate and oxalate is highly dependent on allosteric activation by extracellular chloride or nonsubstrate anions. Extracellular chloride stimulates apparent Vmax of human SLC26A1-mediated sulfate uptake by conferring a two-log decrease in sensitivity to inhibition by extracellular protons, without changing transporter affinity for extracellular sulfate. In contrast to SLC26A1-mediated sulfate transport, SLC26A1-associated chloride transport is activated by acid pHo, shows reduced sensitivity to DIDS, and exhibits cation-dependence of its DIDS-insensitive component. Human SLC26A1 resembles SLC26 paralogs in its inhibition by phorbol ester activation of PKC, which differs in its undiminished polypeptide abundance at or near the oocyte surface. Mutation of SLC26A1 residues corresponding to candidate anion binding site-associated residues in avian SLC26A5/prestin altered anion transport in patterns resembling those of prestin. However, rare SLC26A1 polymorphic variants from a patient with renal Fanconi Syndrome and from a patient with nephrolithiasis/calcinosis exhibited no loss-of-function phenotypes consistent with disease pathogenesis.

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Structure, Function, and Trafficking of SLC4 and SLC26 Anion Transporters

Cited by 53 publications

References 349 publications

Stomatin modulates the activity of the Anion Exchanger 1 (AE1, SLC4A1)

Stomatin modulates the activity of the Anion Exchanger 1 (AE1, SLC4A1)

Deficient acid handling with distal RTA in the NBCe2 knockout mouse

Extracellular Cl− regulates human SO4 2−/anion exchanger SLC26A1 by altering pH sensitivity of anion transport

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