title: NEDD4-2 and salt-sensitive hypertension.
abstract: OBJECTIVE
  NEDD4-2 is an ubiquitin-protein ligase that was originally identified as an interactor of the epithelial Na+ channel (ENaC); this interaction is defective in Liddle's syndrome, causing elevated ENaC activity and salt-sensitive hypertension. In this review we aim to highlight progress achieved in recent years demonstrating that NEDD4-2 is involved in the control of Na+ transporters that are different from ENaC, but which also play a role in salt-sensitive hypertension.
  
  
  RESULTS
  It has been shown that NEDD4-2 interacts with ubiquitylates and negatively regulates the thiazide-sensitive NCC (Na+,Cl- -cotransporter), both in vitro and in vivo in inducible, nephron-specific Nedd4-2 knockout mice. Moreover, evidence has been provided that NEDD4-2 is also involved in the regulation of human NHE3 (Na+,H+-exchanger 3) and NKCC2 (Na+,K+,2Cl- -cotransporter 2).
  
  
  CONCLUSIONS
  The emerging role of NEDD4-2 in the regulation of different Na+ transporters along the nephron and the identification of human polymorphisms in the NEDD4-2 gene (Nedd4L) related to salt-sensitive hypertension makes this ubiquitin-protein ligase an interesting target for the development of antihypertensive drugs.
authors.affiliation: Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Rizzo
authors.forename: Olivier
authors.initials: O
authors.lastname: Staub
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D000075702:Nedd4 Ubiquitin Protein Ligases; D017673:Sodium Chloride, Dietary / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D017673:Sodium Chloride, Dietary; D050608:Sodium-Phosphate Cotransporter Proteins; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618485:Nedd4L protein, human; C000618461:Nedd4l protein, mouse; D044767:Ubiquitin-Protein Ligases