Rescue of tight junctional localization of a claudin-16 mutant D97S by antimalarial medicine primaquine in Madin-Darby canine kidney cells.

ABSTRACT: Magnesium ion (Mg²⁺) is paracellularly reabsorbed through claudin-16 (CLDN16) in the thick ascending limb (TAL) of Henle's loop in the kidney. Genetic disorders of CLDN16 cause mislocalization of CLDN16, resulting in hypomagnesemia. There is no effective treatment for hypomagnesemia except for magnesium administration. Here, we searched for a novel drug to restore tight junctional localization of a CLDN16 mutant. A D97S mutant, which has a mutation in the first extracellular loop (ECL) of CLDN16, was mainly colocalized with endosome marker, whereas wild-type (WT) CLDN16 was colocalized with ZO-1, an adaptor protein of tight junctions. The protein stability of the D97S mutant was lower than that of WT. The expression level of the D97S mutant was increased by lactacystin, a protea

SUBMITTER: Marunaka K 

PROVIDER: S-EPMC6609605 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature