Non-polarized targeting of AE1 causes autosomal dominant distal renal tubular acidosis.
Autosomal dominant distal renal tubular acidosis (ddRTA) is caused by mutations in SLC4A1, which encodes the polytopic chloride-bicarbonate exchanger AE1 that is normally expressed at the basolateral surface of alpha-intercalated cells in the distal nephron. Here we report that, in contrast with many disorders in which mutant membrane proteins are retained intracellularly and degraded, ddRTA can result from aberrant targeting of AE1 to the apical surface.
Devonald
Mark A J
MA
Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital Box 139, Cambridge CB2 2XY, UK.
Smith
Annabel N
AN
Poon
Jenny P
JP
Ihrke
Gudrun
G
Karet
Fiona E
FE
D000141:Acidosis, Renal Tubular / Q000235:genetics* / Q000378:metabolism; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics* / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005799:Genes, Dominant; D006388:Hemagglutinins / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000378:metabolism; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*
D001457:Anion Exchange Protein 1, Erythrocyte; D016827:CD8 Antigens; D015820:Cadherins; D006388:Hemagglutinins; D010446:Peptide Fragments