N. Strutz-Seebohm, G. Seebohm, A.F. Mack, H.-J. Wagner, L. Just, T. Skutella, U.E. Lang, G. Henke, M. Striegel, M. Hollmann, N. Rouach, R.A. Nicoll, J.A. McCormick, J. Wang, D. Pearce, and F. Lang (2005).
Regulation of GluR1 abundance in murine hippocampal neurones by serum- and glucocorticoid-inducible kinase 3.
Journal of Physiology 565(Pt 2): 381-390.
doi: 10.1113/jphysiol.2004.079582
Phosphatidylinositol 3-Kinase (PI3-kinase) is activated during and 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. We show here that, in Xenopus oocytes expressing the AMPA subunit GluR1, SGK3 and to lesser extent SGK2 but not SGK1 increases 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 hybridisation. According to both, Western blotting and immunohistochemistry, 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.