Regulation of GluR1 abundance in murine hippocampal neurones by serum- and glucocorticoid-inducible kinase 3 |
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| Authors: | Nathalie Strutz-Seebohm Guiscard Seebohm reas F. Mack Hans-Joachim Wagner Lothar Just Thomas Skutella Undine E. Lang Guido Henke Marion Striegel Michael Hollmann Nathalie Rouach Roger A. Nicoll James A. McCormick Jian Wang David Pearce Florian Lang |
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| Affiliation: | Department of Physiology I, University of Tuebingen, D-72076 Tuebingen, Germany;Department of Anatomy, University of Tuebingen, D-72074 Tuebingen, Germany;Department of Psychiatry, CharitéMedicine, D-14050 Berlin, Germany;Department of Biochemistry I –Receptor Biochemistry, Ruhr University Bochum, D-44780 Bochum, Germany;Departments of Cellular and Molecular Pharmacology and Physiology, University of, California, San Francisco, CA 94143, USA;Division of Nephrology, Departments of Medicine and of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-0532, USA |
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| Abstract: | Phosphatidylinositol 3 kinase (PI3-kinase) is activated during and is required for hippocampal glutamate receptor-dependent long-term potentiation. It mediates the delivery of AMPA receptors to the neuronal surface. Among the downstream targets of PI3-kinase are three members of the serum- and glucocorticoid-inducible kinase family, SGK1, SGK2 and SGK3. In Xenopus oocytes expressing the AMPA subunit GluR1, we show that SGK3, and to a lesser extent SGK2, but not SGK1, increase glutamate-induced currents by increasing the abundance of GluR1 protein in the cell membrane. We further show Sgk3 mRNA expression in the hippocampus by RT-PCR and in situ hybridization. According to Western blotting, the hippocampal abundance of GluR1 is significantly lower in gene-targeted mice lacking SGK3 ( Sgk3 −/−) than in their wild-type littermates ( Sgk3 +/+). The present observations disclose a novel mechanism in the regulation of GluR1. |
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