Ae4 (Slc4a9) is an electroneutral monovalent cation-dependent Cl−/HCO3− exchanger

Peña-Münzenmayer, Gaspar; George, Alvin; Shull, Gary E.; Melvin, James E.; Catalán, Marcelo A.

doi:10.1085/jgp.201611571

Cited by 40 publications

(48 citation statements)

References 42 publications

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“…CHO-K1 cells (Sigma-Aldrich) were maintained as described previously (48). Plasmids encoding Mus musculus Slc26a6 (GenBank accession no.…”

Section: Cell Culture and Transfectionsmentioning

confidence: 99%

“…After dispersion and dye loading, acinar cells were rinsed and resuspended in 5 ml of BME at 37°C. Plasmid-transfected CHO-K1 cells were loaded with SPQ using a hypotonic loading buffer, as described previously (48). In brief, cells attached to a coverglass were incubated in a 150 mOsm hypotonic solution containing 5 mM SPQ for 4 min at 23°C.…”

Section: Intracellular CL ؊ and Ph Measurementsmentioning

confidence: 99%

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The apical anion exchanger Slc26a6 promotes oxalate secretion by murine submandibular gland acinar cells

Mukaibo

Munemasa

George³

et al. 2018

Journal of Biological Chemistry

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The solute carrier family 26 () gene family encodes at least 10 different anion exchangers. SLC26 member 6 (SLC26A6 or CFEX/PAT-1) and the cystic fibrosis transmembrane conductance regulator (CFTR) co-localize to the apical membrane of pancreatic duct cells, where they act in concert to drive HCO and fluid secretion. In contrast, in the small intestine, SLC26A6 serves as the major pathway for oxalate secretion. However, little is known about the function of Slc26a6 in murine salivary glands. Here, RNA sequencing-based transcriptional profiling and Western blots revealed that is highly expressed in mouse submandibular and sublingual salivary glands. Slc26a6 localized to the apical membrane of salivary gland acinar cells with no detectable immunostaining in the ducts. CHO-K1 cells transfected with mouse exchanged Cl for oxalate and HCO, whereas two other anion exchangers known to be expressed in salivary gland acinar cells, Slc4a4 and Slc4a9, mediated little, if any, Cl/oxalate exchange. Of note, both Cl/oxalate exchange and Cl/HCO exchange were significantly reduced in acinar cells isolated from the submandibular glands of mice. Oxalate secretion in submandibular saliva also decreased significantly in mice, but HCO secretion was unaffected. Taken together, our findings indicate that Slc26a6 is located at the apical membrane of salivary gland acinar cells, where it mediates Cl/oxalate exchange and plays a critical role in the secretion of oxalate into saliva.

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“…CHO-K1 cells (Sigma-Aldrich) were maintained as described previously (48). Plasmids encoding Mus musculus Slc26a6 (GenBank accession no.…”

Section: Cell Culture and Transfectionsmentioning

confidence: 99%

Section: Intracellular CL ؊ and Ph Measurementsmentioning

confidence: 99%

The apical anion exchanger Slc26a6 promotes oxalate secretion by murine submandibular gland acinar cells

Mukaibo

Munemasa

George³

et al. 2018

Journal of Biological Chemistry

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“…Na + -driven Cl -/HCO 3 exchanger, or a Na + -HCO 3 cotransporter (8,35,61,83). A recent study suggests that AE4 may be an electroneutral, nonselective cation-dependent Cl -/HCO 3 exchanger (61).…”

Section: Na + Reabsorption Across Principal Cellsmentioning

confidence: 99%

Versatility of NaCl transport mechanisms in the cortical collecting duct

Edwards

Crambert

2017

American Journal of Physiology-Renal Physiology

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The cortical collecting duct (CCD) forms part of the aldosterone-sensitive distal nephron and plays an essential role in maintaining the NaCl balance and acid-base status. The CCD epithelium comprises principal cells as well as different types of intercalated cells. Until recently, transcellular Na transport was thought to be restricted to principal cells, whereas (acid-secreting) type A and (bicarbonate-secreting) type B intercalated cells were associated with the regulation of acid-base homeostasis. This review describes how this traditional view has been upended by several discoveries in the past decade. A series of studies has shown that type B intercalated cells can mediate electroneutral NaCl reabsorption by a mechanism involving Na-dependent and Na-independent Cl/[Formula: see text] exchange, and that is energetically driven by basolateral vacuolar H-ATPase pumps. Other research indicates that type A intercalated cells can mediate NaCl secretion, through a bumetanide-sensitive pathway that is energized by apical H,K-ATPase type 2 pumps operating as Na/K exchangers. We also review recent findings on the contribution of the paracellular route to NaCl transport in the CCD. Last, we describe cross-talk processes, by which one CCD cell type impacts Na/Cl transport in another cell type. The mechanisms that have been identified to date demonstrate clearly the interdependence of NaCl and acid-base transport systems in the CCD. They also highlight the remarkable versatility of this nephron segment.

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“…e human SLC4 family consists of 10 genes encoding secondary transporters for bicarbonate and/or carbonate [83,84]. e SLC4 family is divided into three major branches: electrically neutral Na + -independent Cl − /HCO 3 − antiporters, including SLC4A1 (AE1), SLC4A2 (AE2), and SLC4A3 (AE3); Na + -dependent SLC4 HCO 3 − transporters, including electricity-producing SLC4A4 (NBCe1) and SLC4A5 (NBCe2), electrically neutral Na + /HCO 3 − cotransporters SLC4A7 (NBCn1) and SLC4A10 (NBCn2), and a Na + -2HCO 3 − /Cl − exchanger; and a branch with one unusual member (SLC4A9) that has been described as being capable of most of the above actions [83,[85][86][87]. Here, we discuss the most significant Cl − /HCO 3 − antiporters, AE1 and AE2, in the stomach.…”

Section: Physiological Function Of the Slc4 Family In The Stomachmentioning

confidence: 99%

Physiological Significance of Ion Transporters and Channels in the Stomach and Pathophysiological Relevance in Gastric Cancer

Yuan

Tuo

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Gastric cancer (GC) is a highly invasive and fatal malignant disease that accounts for 5.7% of new global cancer cases and is the third leading cause of cancer-related death. Acid/base homeostasis is critical for organisms because protein and enzyme function, cellular structure, and plasma membrane permeability change with pH. Various ion transporters are expressed in normal gastric mucosal epithelial cells and regulate gastric acid secretion, ion transport, and fluid absorption, thereby stabilizing the differentiation and homeostasis of gastric mucosal epithelial cells. Ion transporter dysfunction results in disordered ion transport, mucosa barrier dysfunction, and acid/base disturbances, causing gastric acid-related diseases such as chronic atrophic gastritis (CAG) and GC. This review summarizes the physiological functions of multiple ion transporters and channels in the stomach, including Cl− channels, Cl−/HCO3− exchangers, sodium/hydrogen exchangers (NHEs), and potassium (K+) channels, and their pathophysiological relevance in GC.

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Ae4 (Slc4a9) is an electroneutral monovalent cation-dependent Cl−/HCO3− exchanger

Abstract: AE4 is an anion exchanger known to counter transport Cl− and HCO3− across secretory cell membranes. Peña-Münzenmayer et al. show that AE4 is an electroneutral exchanger and that it also transports monovalent cations in the same direction as HCO3−.

Cited by 40 publications

References 42 publications

The apical anion exchanger Slc26a6 promotes oxalate secretion by murine submandibular gland acinar cells

The apical anion exchanger Slc26a6 promotes oxalate secretion by murine submandibular gland acinar cells

Versatility of NaCl transport mechanisms in the cortical collecting duct

Physiological Significance of Ion Transporters and Channels in the Stomach and Pathophysiological Relevance in Gastric Cancer

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