This review was presented at The Journal of Physiology Symposium on Regulation of neuronal cell volume: From activation to inhibition to degeneration, which took place at Experimental Biology 2010, Anaheim, CA, USA, 26 April 2010. It was commissioned by the Editorial Board and reflects the views of the authors.
Significance of SGK1 in the regulation of neuronal function
Article first published online: 16 SEP 2010
© 2010 The Authors. Journal compilation © 2010 The Physiological Society
The Journal of Physiology
Volume 588, Issue 18, pages 3349–3354, September 2010
How to Cite
Lang, F., Strutz-Seebohm, N., Seebohm, G. and Lang, U. E. (2010), Significance of SGK1 in the regulation of neuronal function. The Journal of Physiology, 588: 3349–3354. doi: 10.1113/jphysiol.2010.190926
- Issue published online: 16 SEP 2010
- Article first published online: 16 SEP 2010
- (Received 1 April 2010; accepted after revision 6 June 2010; first published online 7 June 2010)
The present brief review highlights the putative role of the serum- and glucocorticoid-inducible-kinase-1 (SGK1) in the regulation of neuronal function. SGK1 is genomically upregulated by cell shrinkage and by a variety of hormones including mineralocorticoids and glucocorticoids. The kinase is activated by insulin and growth factors via phosphatidylinositide-3-kinase (PI3-kinase), phosphoinositide-dependent kinase PDK1 and mammalian target of rapamycin mTORC2. SGK1 upregulates ion channels (e.g. SCN5A, ENaC, ASIC1, TRPV5,6, ROMK, Kv1.1–5, KCNEx/KCNQ1–5, GluR6, VSOAC, ClC2, CFTR), carriers (e.g. NHE3, NKCC2, NCC, NaPiIIb, SMIT, GLUT1,4, SGLT1, NaDC, EAAT1–5, SN1, ASCT2, 4F2/LAT, PepT2), and the Na+/K+-ATPase. SGK1 regulates enzymes (e.g. glycogen-synthase-kinase-3, ubiquitin-ligase Nedd4-2, phosphomannose-mutase-2), and transcription factors (e.g. forkhead transcription factor Foxo3a, β-catenin, nuclear factor-kappa-B (NFκB)). SGK1 participates in the regulation of transport, hormone release, neuroexcitability, inflammation, coagulation, cell proliferation and apoptosis. SGK1 contributes to regulation of renal Na+ retention, renal K+ elimination, salt appetite, gastric acid secretion, intestinal Na+/H+ exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Presumably, SGK1 contributes to the regulation of diverse cerebral functions (e.g. memory consolidation, fear retention) and the pathophysiology of several cerebral diseases (e.g. Parkinson's disease, schizophrenia, depression, Alzheimer's disease). Despite multiple SGK1 functions, the phenotype of the SGK1 knockout mouse is mild and becomes only apparent under challenging conditions.