Endoplasmic reticulum-associated degradation of the renal potassium channel, ROMK, leads to type II Bartter syndrome.

ABSTRACT: Type II Bartter syndrome is caused by mutations in the renal outer medullary potassium (ROMK) channel, but the molecular mechanisms underlying this disease are poorly defined. To rapidly screen for ROMK function, we developed a yeast expression system and discovered that yeast cells lacking endogenous potassium channels could be rescued by WT ROMK but not by ROMK proteins containing any one of four Bartter mutations. We also found that the mutant proteins were significantly less stable than WT ROMK. However, their degradation was slowed in the presence of a proteasome inhibitor or when yeast cells contained mutations in the CDC48 or SSA1 gene, which is required for endoplasmic reticulum (ER)-associated degradation (ERAD). Consistent with these data, sucrose gradient centrifug

SUBMITTER: O'Donnell BM 

PROVIDER: S-EPMC5546024 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature