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1 Department of Physiology I, University of Tuebingen, Tuebingen, Germany
2 Department of Anatomy, University of Tuebingen, Tuebingen, Germany
3 Department of Biochemistry I – Receptor Biochemistry, Ruhr University Bochum, Bochum, Germany
Generation of memory is enhanced during stress, an effect attributed to stimulation of neuronal learning by adrenal glucocorticoids. The glucocorticoid-dependent genes include the serum- and glucocorticoid-inducible kinase SGK1. SGK1 is activated through the phosphatidylinositol 3 kinase (PI3-kinase) pathway by growth factors such as insulin-like growth factor-1 (IGF1) or tumour growth factor ß (TGF-ß). Previously, a fourfold higher expression of SGK1 has been observed in fast-learning rats as compared with slow-learning rats. The mechanisms linking glucocorticoids or SGK1 with neuronal function have, however, remained elusive. We show here that treatment of mice with the glucocorticoid dexamethasone (238 µg day–1 for 8–20 days) enhances hippocampal expression of GluR6. Immunohistochemistry reveals significantly enhanced GluR6 protein abundance at neurones but not at astrocytes in mice. Immunohistochemistry and patch clamp on hippocampal neurones in primary culture reveal upregulation of GluR6 protein abundance and kainate-induced currents following treatment with dexamethasone (1 µM) and TGF-ß (1 µM). In Xenopus oocytes expressing rat GluR6, coexpression of SGK1 strongly increases glutamate-induced current at least partially by increasing the abundance of GluR6 protein in the plasma membrane. The related kinases SGK2 and SGK3 similarly stimulate GluR6, but are less effective than SGK1. The observations point to a novel mechanism regulating GluR6 which contributes to the regulation of neuronal function by glucocorticoids.
(Received 19 November 2004;
accepted after revision 17 March 2005;
first published online 17 March 2005)
Corresponding author F. Lang: Department of Physiology I, University of Tuebingen, 72076 Tuebingen, Germany. Email: florian.lang{at}uni-tuebingen.de
This article has been cited by other articles:
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  F. Lang, C. Bohmer, M. Palmada, G. Seebohm, N. Strutz-Seebohm, and V. Vallon (Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms. Physiol Rev, October 1, 2006; 86(4): 1151 - 1178. [Abstract] [Full Text] [PDF]
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 N. Strutz-Seebohm, G. Seebohm, A. F. Mack, H.-J. Wagner, L. Just, T. Skutella, U. E. Lang, G. Henke, M. Striegel, M. Hollmann, et al. Regulation of GluR1 abundance in murine hippocampal neurones by serum- and glucocorticoid-inducible kinase 3 J. Physiol., June 1, 2005; 565(2): 381 - 390. [Abstract] [Full Text] [PDF]
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