RESUMO
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, 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.
Assuntos
Proteína 1 de Troca de Ânion do Eritrócito , Processamento de Proteína Pós-Traducional , Animais , Humanos , Proteína 1 de Troca de Ânion do Eritrócito/genética , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Mutação , Processamento de Proteína Pós-Traducional/genéticaRESUMO
Urinary tract infections affect more than 1 in 2 women during their lifetime. Among these, more than 10% of patients carry antibiotic-resistant bacterial strains, highlighting the urgent need to identify alternative treatments. While innate defense mechanisms are well-characterized in the lower urinary tract, it is becoming evident that the collecting duct (CD), the first renal segment encountered by invading uropathogenic bacteria, also contributes to bacterial clearance. However, the role of this segment is beginning to be understood. This review summarizes the current knowledge on CD intercalated cells in urinary tract bacterial clearance. Understanding the innate protective role of the uroepithelium and of the CD offers new opportunities for alternative therapeutic strategies.