Functional rescue of a kidney anion exchanger 1 trafficking mutant in renal epithelial cells

PLoS One. 2013;8(2):e57062. doi: 10.1371/journal.pone.0057062. Epub 2013 Feb 27.


Mutations in the SLC4A1 gene encoding the anion exchanger 1 (AE1) can cause distal renal tubular acidosis (dRTA), a disease often due to mis-trafficking of the mutant protein. In this study, we investigated whether trafficking of a Golgi-retained dRTA mutant, G701D kAE1, or two dRTA mutants retained in the endoplasmic reticulum, C479W and R589H kAE1, could be functionally rescued to the plasma membrane of Madin-Darby Canine Kidney (MDCK) cells. Treatments with DMSO, glycerol, the corrector VX-809, or low temperature incubations restored the basolateral trafficking of G701D kAE1 mutant. These treatments had no significant rescuing effect on trafficking of the mis-folded C479W or R589H kAE1 mutants. DMSO was the only treatment that partially restored G701D kAE1 function in the plasma membrane of MDCK cells. Our experiments show that trafficking of intracellularly retained dRTA kAE1 mutants can be partially restored, and that one chemical treatment rescued both trafficking and function of a dRTA mutant. These studies provide an opportunity to develop alternative therapeutic solutions for dRTA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / pharmacology
  • Animals
  • Anion Exchange Protein 1, Erythrocyte / biosynthesis
  • Anion Exchange Protein 1, Erythrocyte / genetics*
  • Anion Exchange Protein 1, Erythrocyte / metabolism*
  • Benzodioxoles / pharmacology
  • Dimethyl Sulfoxide / pharmacology
  • Dogs
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • HEK293 Cells
  • Humans
  • Kidney / cytology*
  • Madin Darby Canine Kidney Cells
  • Mutant Proteins / biosynthesis
  • Mutant Proteins / metabolism*
  • Mutation / genetics*
  • Protein Biosynthesis / drug effects
  • Protein Transport / drug effects
  • Temperature


  • Aminopyridines
  • Anion Exchange Protein 1, Erythrocyte
  • Benzodioxoles
  • Mutant Proteins
  • SLC4A1 protein, human
  • lumacaftor
  • Dimethyl Sulfoxide