title: The role of the ENaC-regulatory complex in aldosterone-mediated sodium transport.
abstract: 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.
authors.affiliation: Division of Nephrology, Department of Medicine, University of California-San Francisco, CA 94143, USA.
authors.forename: Rama
authors.initials: R
authors.lastname: Soundararajan
authors.forename: David
authors.initials: D
authors.lastname: Pearce
authors.forename: Tim
authors.initials: T
authors.lastname: Ziera
mesh_terms: D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000450:Aldosterone; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D017346:Protein Serine-Threonine Kinases; D012964:Sodium; D014157:Transcription Factors; D000099184:Serum-Glucocorticoid Regulated Kinases; C496471:CNKSR3 protein, human; C404226:TSC22D3 protein, human
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