Abstract
Ubiquitylation is crucial for regulating numerous cellular functions. In the kidney, ubiquitylation regulates the epithelial Na(+) channel ENaC. The importance of this process is highlighted in Liddle's syndrome, where mutations interfere with ENaC ubiquitylation, resulting in constitutive Na(+) reabsorption and hypertension. There is emerging evidence that NCC, involved in hypertensive diseases, is also regulated by ubiquitylation. Here, we discuss the current knowledge and recent findings in this field.
Highlights
Hypertension is involved in many diseases like stroke, myocardial infarction, heart and kidney failure
The WNK region, which interacts with KLHL3, is that mutated in PHAII [67, 88]. Taken all these data together, we propose a model for the differential effect of ubiquitylation via NEDD4-2 or via KLHL3/Cullin 3 (CUL3) on NaCl cotransporter (NCC) regulation in normal and pathological conditions (Figure 2)
As discussed very recently by Ellison [20], there is more and more evidence suggesting that the absence of NEDD4-2-mediated ubiquitylation is not a prerequisite for upregulating epithelial Na+ channel (ENaC) [5, 78]
Summary
Hypertension is involved in many diseases like stroke, myocardial infarction, heart and kidney failure. The groups of Lifton and Jeunemaître have independently shown that mutations in humans affecting the genes encoding the kelch-like KLHL3/Cullin 3 (CUL3) ubiquitin-protein ligase complex lead to overactive NCC and hypertension [9, 48], pointing at the importance of ubiquitylation in the regulation of renal Na+ transport.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
