Regulation of the excitatory amino acid transporter EAAT5 by the serum and glucocorticoid dependent kinases SGK1 and SGK3.
In the mammalian retina, glutamate re-uptake is mediated by the sodium dependent cotransport systems EAAT1-5 thus terminating neuronal excitation and preventing neuroexcitotoxicity. In retinal amacrine and ganglion cells, EAAT5 is colocalized with the serum and glucocorticoid inducible kinase SGK1, a serine/threonine kinase known to regulate transport. The study explored the possible regulation of EAAT5 by SGK1, its isoform SGK3, and the closely related protein kinase B. EAAT5 was coexpressed in Xenopus laevis oocytes with or without the respective kinases. Transport activity was quantified by electrophysiology and cell surface expression was determined by chemiluminescence. Both EAAT5 mediated currents and EAAT5 protein abundance at the cell surface were increased by a factor of 1.5-2 upon coexpression of SGK1 or SGK3 but not following coexpression of PKB. In conclusion, the kinases SGK1 and SGK3 increase EAAT5 activity by increasing cell surface abundance of the carrier.
Boehmer
Christoph
C
Department of Physiology I, Eberhard-Karls-University of Tübingen, Tübingen, Germany.
Rajamanickam
Jeyaganesh
J
Schniepp
Roman
R
Kohler
Konrad
K
Wulff
Peer
P
Kuhl
Dietmar
D
Palmada
Monica
M
Lang
Florian
F
D019943:Amino Acid Substitution; D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D050582:Excitatory Amino Acid Transporter 5; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins; D008564:Membrane Potentials / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology*; D010786:Photoreceptor Cells / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis; D000099184:Serum-Glucocorticoid Regulated Kinases
D026905:Amino Acid Transport Systems; D050582:Excitatory Amino Acid Transporter 5; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins; D000099184:Serum-Glucocorticoid Regulated Kinases; C105645:SLC1A7 protein, human