ArticleThe Journal of physiology2015
Essential role of carbonic anhydrase XII in secretory gland fluid and HCO3 (-) secretion revealed by disease causing human mutation.
Article in The Journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.Nature communications · 2019Pooled it
- Loss of CA12 drive proliferation and fibrosis in type i congenital pulmonary airway malformation via promoting abnormal activation of SHH signaling.Cell communication and signaling : CCS · 2026Article
- Article
- Salivary gland carbonic anhydrases.Histology and histopathology · 2025Review
- Lipid transporters E-Syt3 and ORP5 regulate epithelial ion transport by controlling phosphatidylserine enrichment at ER/PM junctions.The EMBO journal · 2025Article
- Structure based exploration of mitochondrial alpha carbonic anhydrase inhibitors as potential leads for anti-obesity drug development.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Review
- Multiple Regulatory Signals and Components in the Modulation of Bicarbonate Transporters.Pharmaceutics · 2024Review
- Trafficking of carbonic anhydrase 12 and bicarbonate transporters by histamine stimulation mediates intracellular acidic scenario in lung cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- 4-(3-Phenyl-4-(3,4,5-trimethoxybenzoyl)-1Journal of medicinal chemistry · 2023Article
- Ultrafast and selective labeling of endogenous proteins using affinity-based benzotriazole chemistry.Chemical science · 2022Article
- Review
- Case Report: NovelFrontiers in pediatrics · 2022Article
- jSRC: a flexible and accurate joint learning algorithm for clustering of single-cell RNA-sequencing data.Briefings in bioinformatics · 2021Article
- Large pH oscillations promote host defense against human airways infection.The Journal of experimental medicine · 2021Article
- Carbonic Anhydrases as Potential Targets Against Neurovascular Unit Dysfunction in Alzheimer's Disease and Stroke.Frontiers in aging neuroscience · 2021Review
- Targeting the pH Paradigm at the Bedside: A Practical Approach.International journal of molecular sciences · 2020Review
- Human carbonic anhydrases and post-translational modifications: a hidden world possibly affecting protein properties and functions.Journal of enzyme inhibition and medicinal chemistry · 2020Review
- Carbonic Anhydrase Sensitivity to Pesticides: Perspectives for Biomarker Development.International journal of molecular sciences · 2020Review
- Review
- The Fundamental Role of Bicarbonate Transporters and Associated Carbonic Anhydrase Enzymes in Maintaining Ion and pH Homeostasis in Non-Secretory Organs.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
key pointsFluid and HCO3 (-) secretion is essential for all epithelia; aberrant secretion is associated with several diseases. Carbonic anhydrase XII (CA12) is the key carbonic anhydrase in epithelial fluid and HCO3 (-) secretion and works by activating the ductal Cl(-) -HCO3 (-) exchanger AE2. Delivery of CA12 to salivary glands increases salivation in mice and of the human mutation CA12(E143K) markedly inhibits it. The human mutation CA12(E143K) causes disease due to aberrant CA12 glycosylation, and misfolding resulting in loss of AE2 activity. ABSTRACT: Aberrant epithelial fluid and HCO3 (-) secretion is associated with many diseases. The activity of HCO3 (-) transporters depends of HCO3 (-) availability that is determined by carbonic anhydrases (CAs). Which CAs are essential for epithelial function is unknown. CA12 stands out since the CA12(E143K) mutation causes salt wasting in sweat and dehydration in humans. Here, we report that expression of CA12 and of CA12(E143K) in mice salivary glands respectively increased and prominently inhibited ductal fluid secretion and salivation in vivo. CA12 markedly increases the activity and is the major HCO3 (-) supplier of ductal Cl(-) -HCO3 (-) exchanger AE2, but not of NBCe1-B. The E143K mutation alters CA12 glycosylation at N28 and N80, resulting in retention of the basolateral CA12 in the ER. Knockdown of AE2 and of CA12 inhibited pancreatic and salivary gland ductal AE2 activity and fluid secretion. Accordingly, patients homozygous for the CA12(E143K) mutation have a dry mouth, dry tongue phenotype. These findings reveal an unsuspected prominent role of CA12 in epithelial function, explain the disease and call for caution in the use of CA12 inhibitors in cancer treatment.
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