Functional Rescue of a Kidney Anion Exchanger 1 Trafficking Mutant in Renal Epithelial Cells

Autor: Emmanuelle Cordat, Mattia Berrini, R. Todd Alexander, Jennifer C. King, Carmen Y. S. Chu
Rok vydání: 2013
Předmět:
Protein Folding
Anatomy and Physiology
Mutant
Aminopyridines
lcsh:Medicine
Kidney
Antiport Proteins
medicine.disease_cause
Biochemistry
Madin Darby Canine Kidney Cells
Transmembrane Transport Proteins
Distal renal tubular acidosis
Mutant protein
Anion Exchange Protein 1
Erythrocyte
Molecular Cell Biology
lcsh:Science
0303 health sciences
Mutation
Multidisciplinary
Physics
030302 biochemistry & molecular biology
Temperature
Transport protein
Cell biology
Protein Transport
medicine.anatomical_structure
Membranes and Sorting
Research Article
Cell Physiology
Biophysics
Biology
03 medical and health sciences
Dogs
medicine
Animals
Humans
Dimethyl Sulfoxide
Benzodioxoles
030304 developmental biology
Renal Physiology
Endoplasmic reticulum
lcsh:R
HEK 293 cells
Proteins
Epithelial Cells
Renal System
medicine.disease
Molecular biology
HEK293 Cells
Protein Biosynthesis
Mutant Proteins
lcsh:Q
Zdroj: PLoS ONE, Vol 8, Iss 2, p e57062 (2013)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0057062
Popis: 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.
Databáze: OpenAIRE
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