The carboxyl-terminally truncated kidney anion exchanger 1 R901X dRTA mutant is unstable at the plasma membrane
| Autor: | R. Todd Alexander, Rawad Lashhab, Emmanuelle Cordat, Ensaf Y. Almomani |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Swine Physiology Mutant Biology Kidney Endocytosis Cell Line Cell membrane Structure-Activity Relationship 03 medical and health sciences Distal renal tubular acidosis Anion Exchange Protein 1 Erythrocyte medicine Animals Humans Endomembrane system Epithelial polarity 030102 biochemistry & molecular biology Cell Membrane Epithelial Cells Cell Biology medicine.disease Cell biology HEK293 Cells 030104 developmental biology medicine.anatomical_structure Membrane protein Biochemistry Mutation |
| Zdroj: | American Journal of Physiology-Cell Physiology. 310:C764-C772 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00305.2015 |
| Popis: | Mutations in the SLC4A1 gene coding for kidney anion exchanger 1 (kAE1) cause distal renal tubular acidosis (dRTA). We investigated the fate of the most common truncated dominant dRTA mutant kAE1 R901X. In renal epithelial cells, we found that kAE1 R901X is less abundant than kAE1 wild-type (WT) at the plasma membrane. Although kAE1 WT and kAE1 R901X have similar half-lives, the decreased abundance of kAE1 R901X at the surface is due to an increased endocytosis rate and a decreased recycling rate of endocytosed proteins. We propose that, in polarized renal epithelial cells, the apically mistargeted kAE1 R901X mutant is endocytosed faster than kAE1 WT and its recycling to the basolateral membrane is delayed. This resets the equilibrium, such that kAE1 R901X resides predominantly in an endomembrane compartment, thereby likely participating in development of dRTA disease. |
| Databáze: | OpenAIRE |
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