TY - JOUR
T1 - The role of the ENaC-regulatory complex in aldosterone-mediated sodium transport
AU - Soundararajan, Rama
AU - Pearce, David
AU - Ziera, Tim
N1 - Funding Information:
This work is supported by National Institutes of Health grants K01-DK078679 (to RS), R01-DK56695 (to DP), and R01-DK85101 (to DP).
PY - 2012/3/24
Y1 - 2012/3/24
N2 - The mineralocorticoid aldosterone is indispensable for the control of blood pressure and fluid volume in mammals. It acts in large part to increase the abundance and activity of the epithelial Na + channel (ENaC), which mediates apical Na + entry in the distal parts of the kidney tubules. Aldosterone acts through the mineralocorticoid receptor to alter the transcription of specific genes, including SGK1 and GILZ1. Recent evidence suggests that these key aldosterone-regulated factors function within a unique multi-protein ENaC-regulatory-complex that governs the net cell surface expression and activity of the channel. Another aldosterone-induced protein, CNK3 (connector enhancer of kinase suppressor of Ras 3), also stimulates ENaC and has all of the features of a scaffolding protein. With these observations in mind, we discuss the possibility that CNK3 coordinates the dynamic assembly of the ENaC-regulatory-complex, and promotes context-appropriate aldosterone signal transduction in the regulation of epithelial Na + transport.
AB - The mineralocorticoid aldosterone is indispensable for the control of blood pressure and fluid volume in mammals. It acts in large part to increase the abundance and activity of the epithelial Na + channel (ENaC), which mediates apical Na + entry in the distal parts of the kidney tubules. Aldosterone acts through the mineralocorticoid receptor to alter the transcription of specific genes, including SGK1 and GILZ1. Recent evidence suggests that these key aldosterone-regulated factors function within a unique multi-protein ENaC-regulatory-complex that governs the net cell surface expression and activity of the channel. Another aldosterone-induced protein, CNK3 (connector enhancer of kinase suppressor of Ras 3), also stimulates ENaC and has all of the features of a scaffolding protein. With these observations in mind, we discuss the possibility that CNK3 coordinates the dynamic assembly of the ENaC-regulatory-complex, and promotes context-appropriate aldosterone signal transduction in the regulation of epithelial Na + transport.
KW - Aldosterone signaling
KW - ENaC-regulatory complex
KW - Scaffold protein
UR - http://www.scopus.com/inward/record.url?scp=84856349666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856349666&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2011.11.003
DO - 10.1016/j.mce.2011.11.003
M3 - Review article
C2 - 22101317
AN - SCOPUS:84856349666
SN - 0303-7207
VL - 350
SP - 242
EP - 247
JO - Molecular and cellular endocrinology
JF - Molecular and cellular endocrinology
IS - 2
ER -