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Unraveling the Molecular Landscape of kAE1: A Narrative Review.
Canadian Journal of Physiology and Pharmacology 2024 April 27
Kidney anion exchanger 1 (kAE1) is an isoform of the AE1 protein encoded by the SLC4A1 gene. It is a basolateral membrane protein expressed by α-intercalated cells in the connecting tubules and collecting duct of the kidney. Its main function is to exchange bicarbonate and chloride ions between the blood and urine to maintain blood pH at physiological threshold. The kAE1 protein undergoes multiple post-translational modifications such as phosphorylation and ubiquitination and interacts with many different proteins such as claudin-4 and carbonic anhydrase II. Mutations in the gene may lead to the development of distal renal tubular acidosis (dRTA), characterized by the failure to acidify the urine, which may result in nephrocalcinosis and in more severe cases, renal failure. In this review, we discuss the structure and function of kAE1, its post-translational modifications, and protein-protein interactions. Finally we discuss insights gained from the study of kAE1 mutations in humans and in mice.
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