TY - JOUR
T1 - Disinhibitory pathways for control of sodium transport
T2 - Regulation of ENaC by SGK1 and GILZ
AU - Bhalla, Vivek
AU - Soundararajan, Rama
AU - Pao, Alan C.
AU - Li, Hongyan
AU - Pearce, David
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - 14-3-3
KW - ERK
KW - Epithelial sodium channel
KW - Nedd4-2
KW - Trafficking
UR - http://www.scopus.com/inward/record.url?scp=33749391922&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749391922&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00061.2006
DO - 10.1152/ajprenal.00061.2006
M3 - Review article
C2 - 16720863
AN - SCOPUS:33749391922
SN - 1931-857X
VL - 291
SP - F714-F721
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 4
ER -