Ubiquitylation and the pathogenesis of hypertension.
Liddle syndrome is monogenic hypertension caused by mutations in the epithelial Na+ channel (ENaC) that interfere with its ubiquitylation by Nedd4-2. In this issue, Ronzaud and colleagues found that deleting Nedd4-2 from kidney tubules in adult mice led to ENaC accumulation, but not at the plasma membrane, as predicted from current models. Instead, abundance of the sodium chloride transporter NCC increased at the plasma membrane, and the mice have some features of increased NCC activity. Together, the results suggest that defective ubiquitylation of ENaC by Nedd4-2 may not fully explain Liddle syndrome and that Nedd4-2 modulates NCC more strongly.
Division of Nephrology and Hypertension, CH12R, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. ellisond@ohsu.edu
David H
DH
Ellison
D000818:Animals; D056827:Endosomal Sorting Complexes Required for Transport / Q000172:deficiency*; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D007684:Kidney Tubules / Q000503:physiopathology*; D000075702:Nedd4 Ubiquitin Protein Ligases; D011955:Receptors, Drug / Q000378:metabolism*; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency*
D056827:Endosomal Sorting Complexes Required for Transport; D011955:Receptors, Drug; C578875:Slc12a3 protein, mouse; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618485:Nedd4L protein, human; C000618461:Nedd4l protein, mouse; D044767:Ubiquitin-Protein Ligases