Renal COP9 Signalosome Deficiency Alters CUL3-KLHL3-WNK Signaling Pathway.

ABSTRACT:

Background

The familial hyperkalemic hypertension (FHHt) cullin 3 (CUL3) mutant does not degrade WNK kinases normally, thereby leading to thiazide-sensitive Na-Cl cotransporter (NCC) activation. CUL3 mutant (CUL3Δ9) does not bind normally to the COP9 signalosome (CSN), a deneddylase involved in regulating cullin-RING ligases. CUL3Δ9 also caused increased degradation of the CUL3-WNK substrate adaptor kelch-like 3 (KLHL3). Here, we sought to determine how defective CSN action contributes to the CUL3Δ9 phenotype.

Methods

The Pax8/LC1 mouse system was used to generate mice in which the catalytically active CSN subunit, Jab1, was deleted only along the nephron, after full development (KS-Jab1 ^-/-).

Results

Western blot analysis

SUBMITTER: Cornelius RJ 

PROVIDER: S-EPMC6218864 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature