Mutations associated with Dent's disease affect gating and voltage dependence of the human anion/proton exchanger ClC-5.

ABSTRACT: Dent's disease is associated with impaired renal endocytosis and endosomal acidification. It is linked to mutations in the membrane chloride/proton exchanger ClC-5; however, a direct link between localization in the protein and functional phenotype of the mutants has not been established until now. Here, two Dent's disease mutations, G212A and E267A, were investigated using heterologous expression in HEK293T cells, patch-clamp measurements and confocal imaging. WT and mutant ClC-5 exhibited mixed cell membrane and vesicular distribution. Reduced ion currents were measured for both mutants and both exhibited reduced capability to support endosomal acidification. Functionally, mutation G212A was capable of mediating anion/proton antiport but dramatically shifted the activation of ClC-5 towar

SUBMITTER: Alekov AK 

PROVIDER: S-EPMC4436585 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature