ArticleThe Journal of biological chemistry2015
Ae4 (Slc4a9) Anion Exchanger Drives Cl- Uptake-dependent Fluid Secretion by Mouse Submandibular Gland Acinar Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 38 citations in OpenAlex.
- SLC4A9 deficiency is involved in Sjögren's syndrome and enamel defects through RPS27-triggered ribosomal stress.Experimental & molecular medicine · 2026Article
- Lysophosphatidic Acid (LPA) Salivary Species Detection and Whole-mount LPA Receptor Localization in Mouse Salivary Gland.bioRxiv : the preprint server for biology · 2026Article
- Review
- Molecular determinants of [Formula: see text] and cation transport in the human cation-dependent ClAmerican journal of physiology. Cell physiology · 2025Article
- Selection signatures associated with adaptation in South African Drakensberger, Nguni, and Tuli beef breeds.Tropical animal health and production · 2024Article
- KInternational journal of molecular sciences · 2024Article
- Novel functions of the anion exchanger AE4 (SLC4A9).Pflugers Archiv : European journal of physiology · 2024Review
- The role of NaPflugers Archiv : European journal of physiology · 2024Review
- CFTR expression in human salivary gland acinar cells.American journal of physiology. Cell physiology · 2024Article
- Potential Theranostic Roles of SLC4 Molecules in Human Diseases.International journal of molecular sciences · 2023Review
- Structural and functional analysis of salivary intercalated duct cells reveals a secretory phenotype.The Journal of physiology · 2023Article
- Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney.International journal of molecular sciences · 2023Review
- Salivary gland function, development, and regeneration.Physiological reviews · 2022Review
- Activation of the Ae4 (Slc4a9) cation-driven ClAmerican journal of physiology. Gastrointestinal and liver physiology · 2021Article
- The Bicarbonate Transporter (MoAE4) Localized on Both Cytomembrane and Tonoplast Promotes Pathogenesis inJournal of fungi (Basel, Switzerland) · 2021Article
- Calcium Dynamics and Water Transport in Salivary Acinar Cells.Bulletin of mathematical biology · 2021Review
- Slc4a11 disruption causes duct cell loss and impairs NaCl reabsorption in female mouse submandibular glands.Physiological reports · 2019Article
- Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations.Science advances · 2019Article
- The apical NaJournal of cellular physiology · 2019Article
- A Mathematical Model of Fluid Transport in an Accurate Reconstruction of Parotid Acinar Cells.Bulletin of mathematical biology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Transcellular Cl(-) movement across acinar cells is the rate-limiting step for salivary gland fluid secretion. Basolateral Nkcc1 Na(+)-K(+)-2Cl(-) cotransporters play a critical role in fluid secretion by promoting the intracellular accumulation of Cl(-) above its equilibrium potential. However, salivation is only partially abolished in the absence of Nkcc1 cotransporter activity, suggesting that another Cl(-) uptake pathway concentrates Cl(-) ions in acinar cells. To identify alternative molecular mechanisms, we studied mice lacking Ae2 and Ae4 Cl(-)/HCO3 (-) exchangers. We found that salivation stimulated by muscarinic and β-adrenergic receptor agonists was normal in the submandibular glands of Ae2(-/-) mice. In contrast, saliva secretion was reduced by 35% in Ae4(-/-) mice. The decrease in salivation was not related to loss of Na(+)-K(+)-2Cl(-) cotransporter or Na(+)/H(+) exchanger activity in Ae4(-/-) mice but correlated with reduced Cl(-) uptake during β-adrenergic receptor activation of cAMP signaling. Direct measurements of Cl(-)/HCO3 (-) exchanger activity revealed that HCO3 (-)-dependent Cl(-) uptake was reduced in the acinar cells of Ae2(-/-) and Ae4(-/-) mice. Moreover, Cl(-)/HCO3 (-) exchanger activity was nearly abolished in double Ae4/Ae2 knock-out mice, suggesting that most of the Cl(-)/HCO3 (-) exchanger activity in submandibular acinar cells depends on Ae2 and Ae4 expression. In conclusion, both Ae2 and Ae4 anion exchangers are functionally expressed in submandibular acinar cells; however, only Ae4 expression appears to be important for cAMP-dependent regulation of fluid secretion.
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