Glutamate down-regulates GLAST expression through AMPA receptors in Bergmann glial cells.
The Na(+)-dependent glutamate/aspartate transporter GLAST plays a major role in the removal of glutamate from the synaptic cleft. Short-, as well as long-term changes in transporter activity are triggered by glutamate. An important locus of regulation is the density of transporter molecules at the plasma membrane. A substrate-dependent change in the translocation rate accounts for the short-term effect, whereas the mechanisms of long-term modulation are less understood. Using cultured chick cerebellar Bergmann glial cells, we report here that glutamate receptors mediate a substantial reduction in GLAST mRNA levels, suggesting a transcriptional level of regulation. Moreover, when the 5' proximal region of the GLAST gene was cloned and transfected into Bergmann glia cells, a decrease in promoter activity was induced by glutamate exposure. The use of specific pharmacological tools established the involvement of Ca(2+)-permeable alpha-amino 3-hydroxy-5-methyl-4-isoaxazolepropionate (AMPA) receptors via protein kinase C and c-Jun. These results demonstrate that GLAST is under transcriptional control through glutamate receptors activation, and further supports the participation of Bergmann glia cells in the modulation of glutamatergic transmission.
López-Bayghen
Esther
E
Departamento de Genética y Biología Molecular, Cinvestav-IPN, Apartado Postal 14-740, Mexico DF, Mexico.
Espinoza-Rojo
Mónica
M
Ortega
Arturo
A
D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000378:metabolism*; D002642:Chick Embryo; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D018698:Glutamic Acid / Q000378:metabolism*; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D027322:Amino Acid Transport System X-AG; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018091:Receptors, AMPA; D018698:Glutamic Acid; D011493:Protein Kinase C