Stimulation of the EAAT4 glutamate transporter by SGK protein kinase isoforms and PKB.
The serum and glucocorticoid inducible kinase (SGK) 1 is expressed in brain tissue and upregulated by ischemia, neuronal excitation, and dehydration. The present study has been performed to elucidate the expression of SGK1 in cerebellar Purkinje cells and to explore whether it influences the colocalized glutamate transporter EAAT4. Intense SGK1 staining was observed in Purkinje cells following 48h of water deprivation. The kinase activates glutamate induced current (I(GLU)) in Xenopus oocytes heterologously expressing EAAT4, an effect mimicked by its isoforms SGK2, 3 and PKB. I(GLU) was decreased by the ubiquitin ligase Nedd4-2, an effect partially but not completely reversed by additional coexpression of the SGK kinase isoforms or PKB. According to immunohistochemistry EAAT4 protein abundance in the cell membrane was enhanced by SGK1 and decreased by Nedd4-2. In conclusion, SGK1 expression is upregulated by ischemia, excitation, and dehydration in cerebellar Purkinje cells. The upregulation of SGK1 may serve to stimulate EAAT4 and thus to reduce neuroexcitotoxicity.
Böhmer
Christoph
C
Department of Physiology, University of Tübingen, Germany.
Philippin
Michaele
M
Rajamanickam
Jeyaganesh
J
Mack
Andreas
A
Broer
Stefan
S
Palmada
Monica
M
Lang
Florian
F
D027322:Amino Acid Transport System X-AG / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D004553:Electric Conductivity; D056827:Endosomal Sorting Complexes Required for Transport; D050581:Excitatory Amino Acid Transporter 4; D050491:Glutamate Plasma Membrane Transport Proteins; D017874:Immediate-Early Proteins; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D000075702:Nedd4 Ubiquitin Protein Ligases; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D011689:Purkinje Cells / Q000737:chemistry / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000032:analysis / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014981:Xenopus; D029867:Xenopus Proteins; D000099184:Serum-Glucocorticoid Regulated Kinases
D027322:Amino Acid Transport System X-AG; D056827:Endosomal Sorting Complexes Required for Transport; D050581:Excitatory Amino Acid Transporter 4; D050491:Glutamate Plasma Membrane Transport Proteins; D017874:Immediate-Early Proteins; D007527:Isoenzymes; D000075702:Nedd4 Ubiquitin Protein Ligases; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D027981:Symporters; D044767:Ubiquitin-Protein Ligases; D029867:Xenopus Proteins; D000099184:Serum-Glucocorticoid Regulated Kinases; C493389:Slc1a6 protein, rat; C000618479:NEDD4L protein, rat; C000618482:Nedd4 protein, Xenopus; C000618484:Nedd4 protein, rat; C000618460:nedd4l protein, Xenopus