1. Cullin 3 mutant causing familial hyperkalemic hypertension lacks normal activity in the kidney
- Author
-
Yujiro Maeoka, Ryan J. Cornelius, Mohammed Zubaerul Ferdaus, Avika Sharma, Luan T. Nguyen, and James A. McCormick
- Subjects
Mice, Knockout ,Aquaporin 2 ,Kelch-Like ECH-Associated Protein 1 ,NF-E2-Related Factor 2 ,Polyuria ,Physiology ,Pseudohypoaldosteronism ,Protein Serine-Threonine Kinases ,Cullin Proteins ,Kidney ,NAD ,Mice ,Cyclin E ,Hypertension ,Animals ,Oxidoreductases ,Biomarkers - Abstract
CUL3 mutation (CUL3-Δ9) causes familial hyperkalemic hypertension (FHHt) by reducing adaptor KLHL3, impairing substrate WNK4 degradation. Whether CUL3-Δ9 affects other targets in kidneys remains unclear. We found that CUL3-Δ9 cannot degrade two CUL3 targets, cyclin E and nuclear factor erythroid-2-related factor 2 (NRF2; using a surrogate marker NQO1), or rescue injury or polyuria caused by Cul3 disruption. In an FHHt model, CUL3-Δ9 impaired NRF2 degradation without reduction of its adaptor KEAP1. Our data provide additional insights into CUL3-Δ9 function in the kidney.
- Published
- 2022