Regulation of GluR1 abundance in murine hippocampal neurones by serum- and glucocorticoid-inducible kinase 3.
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.
Strutz-Seebohm
Nathalie
N
Department of Physiology I, University of Tuebingen, 72076 Tuebingen, Germany.
Seebohm
Guiscard
G
Mack
Andreas F
AF
Wagner
Hans-Joachim
HJ
Just
Lothar
L
Skutella
Thomas
T
Lang
Undine E
UE
Henke
Guido
G
Striegel
Marion
M
Hollmann
Michael
M
Rouach
Nathalie
N
Nicoll
Roger A
RA
McCormick
James A
JA
Wang
Jian
J
Pearce
David
D
Lang
Florian
F
D000818:Animals; D015153:Blotting, Western; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000166:cytology*; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000201:enzymology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009865:Oocytes; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D007527:Isoenzymes; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D018091:Receptors, AMPA; D000099184:Serum-Glucocorticoid Regulated Kinases