title: Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ.
abstract: Regulation of ENaC occurs at several levels. The principal hormonal regulator of ENaC, aldosterone, acts through the mineralocorticoid receptor to modulate ENaC-mediated sodium transport, and considerable attention has focused on defining the components of the early phase of this response. Two genes, SGK1 and GILZ, have now been implicated in this regulation. While the functional significance of SGK1 in mediating aldosterone effects is well established, new evidence has enhanced our understanding of the mechanisms of SGK1 action. In addition, recent work demonstrates a novel role for GILZ in the stimulation of ENaC-mediated sodium transport. Interestingly, both SGK1 and GILZ appear to negatively regulate tonic inhibition of ENaC and thus use disinhibition to propagate the rapid effects of aldosterone to increase sodium reabsorption in tight epithelia.
authors.affiliation: Division of Nephrology, Department of Medicine, University of California, San Francisco, California 94107, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Bhalla
authors.forename: Rama
authors.initials: R
authors.lastname: Soundararajan
authors.forename: Alan C
authors.initials: AC
authors.lastname: Pao
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Pearce
mesh_terms: D000818:Animals; D001692:Biological Transport; D053503:Epithelial Sodium Channels; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D012964:Sodium; D015222:Sodium Channels; D014157:Transcription Factors; D000099184:Serum-Glucocorticoid Regulated Kinases; C404226:TSC22D3 protein, human