Insights into the diverse mechanisms and effects of variant CUL3-induced familial hyperkalemic hypertension

Cell Communication and Signaling

Review

Harish E. Chatrathi¹  Prashant Sharma² 

[1] College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA;NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, USA;

关键词: CUL3;    Hyperkalemia;    Hypertension;    Post-translational modifications;    Substrate-adaptor binding;   

DOI  :  10.1186/s12964-023-01269-z

 received in 2023-05-17, accepted in 2023-08-12,  发布年份 2023

来源: Springer

【 摘 要 】

Familial hyperkalemic hypertension (FHHt), also known as Pseudohypoaldosteronism type II (PHAII) or Gordon syndrome is a rare Mendelian disease classically characterized by hyperkalemia, hyperchloremic metabolic acidosis, and high systolic blood pressure. The most severe form of the disease is caused by autosomal dominant variants in CUL3 (Cullin 3), a critical subunit of the multimeric CUL3-RING ubiquitin ligase complex. The recent identification of a novel FHHt disease variant of CUL3 revealed intricacies within the underlying disease mechanism. When combined with studies on canonical CUL3 variant-induced FHHt, these findings further support CUL3’s role in regulating renal electrolyte transport and maintaining systemic vascular tone. However, the pathophysiological effects of CUL3 variants are often accompanied by diverse systemic disturbances in addition to classical FHHt symptoms. Recent global proteomic analyses provide a rationale for these systemic disturbances, paving the way for future mechanistic studies to reveal how CUL3 variants dysregulate processes outside of the renovascular axis.CZ4fFcoVBmS6Hku-DY98AwVideo Abstract

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 4

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