Carbonic anhydrase 12 mutation modulates membrane stability and volume regulation of aquaporin 5

Patients carrying the carbonic anhydrase12 E143K mutation showed the dry mouth phenotype. The mechanism underlying the modulation of aquaporin 5 and function in the salivary glands by carbonic anhydrase12 remains unknown. In this study, we identified the mislocalised aquaporin 5 in the salivary glan...

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Bibliographic Details
Published in:Journal of enzyme inhibition and medicinal chemistry 2019-01, Vol.34 (1), p.179-188
Main Authors: Hwang, Soyoung, Kang, Jung Yun, Kim, Min Jae, Shin, Dong Min, Hong, Jeong Hee
Format: Article
Language:English
Subjects:
acidosis
Animals
aquaporin 5
Aquaporin 5 - metabolism
Carbonic anhydrase 12
Carbonic Anhydrases - genetics
Carbonic Anhydrases - metabolism
Cell Membrane - enzymology
Cell Size
Enzyme Stability
HEK293 Cells
Humans
Hydrogen-Ion Concentration
Ion Transport
Membrane Transport Proteins - metabolism
Mice, Inbred C57BL
Mutation
Osmolar Concentration
Research Paper
salivary glands
Submandibular Gland - cytology
Submandibular Gland - enzymology
Submandibular Gland - metabolism
volume regulation
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Summary:Patients carrying the carbonic anhydrase12 E143K mutation showed the dry mouth phenotype. The mechanism underlying the modulation of aquaporin 5 and function in the salivary glands by carbonic anhydrase12 remains unknown. In this study, we identified the mislocalised aquaporin 5 in the salivary glands carrying the E143K. The intracellular pH of E143K cells was more acidic than that of the cells carrying wild type. To evaluate the role of carbonic anhydrase12 on the volume regulation of aquaporin 5, the submandibular gland cells were subjected to hypotonic stimuli. E143K enhanced the extent of swelling of cells on hypotonicity. Aquaporin 5 modulates water influx through ion transporters to prevent osmotic imbalance. These results suggest that the carbonic anhydrase12 E143K, including acidification or inflammation, mediates volume dysregulation by the loss of aquaporin 5. Thus, carbonic anhydrase12 may determine sensible effects on the cellular osmotic regulation by modulating aquaporin 5.
ISSN:1475-6366
1475-6374
DOI:10.1080/14756366.2018.1540475