Impact of Nedd4 proteins and serum and glucocorticoid-induced kinases on epithelial Na+ transport in the distal nephron.
The precise control of BP occurs via Na(+) homeostasis and involves the precise regulation of the epithelial Na(+) channel (ENaC) in the aldosterone-sensitive distal nephron. This has been corroborated by the linkage of mutations in the genes encoding ENaC subunits and Liddle's syndrome, a heritable form of human hypertension. Mapping of these mutations on ENaC indicated that inactivation of PY motifs is responsible and leads to the proposition that the channel interacts via its PY motifs with the WW domains of the Nedd4/Nedd4-like ubiquitin-protein ligase family. It is now well established that the cell surface expression of ENaC is controlled via ubiquitylation by this protein family and that this ubiquitylation is regulated by the aldosterone-induced protein serum and glucocorticoid induced kinase 1.
Staub
Olivier
O
Department of Pharmacology & Toxicology, University of Lausanne, Rue du Bugnon 27, 1005 Lausanne, Switzerland. olivier.staub@unil.ch
Verrey
François
F
D001794:Blood Pressure / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D005938:Glucocorticoids / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics; D000075702:Nedd4 Ubiquitin Protein Ligases; D009399:Nephrons / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*
D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D005938:Glucocorticoids; D015222:Sodium Channels; D025801:Ubiquitin; D012964:Sodium; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D044767:Ubiquitin-Protein Ligases