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Glutamate‐dependent transcriptional regulation of GLAST: role of PKC
Author(s) -
LópezBayghen Esther,
Ortega Arturo
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02706.x
Subject(s) - glutamate receptor , protein kinase c , glutamate aspartate transporter , biology , microbiology and biotechnology , neurotransmission , neurotransmitter , metabotropic glutamate receptor 6 , transcriptional regulation , transporter , receptor , chemistry , biochemistry , kinase , metabotropic glutamate receptor , transcription factor , gene
The Na + ‐dependent glutamate/aspartate transporter GLAST plays a major role in the removal of glutamate from the synaptic cleft. Short‐term, as well as long‐term changes in transporter activity are triggered by glutamate. An important locus of regulation is the density of transporter molecules present at the plasma membrane. A substrate‐dependent change in the translocation rate of the transporter molecules accounts for the short‐term effect, whereas the long‐term modulation apparently involves transcriptional regulation. Using cultured chick cerebellar Bergmann glial cells, we report here that glutamate receptors activation mediate a substantial reduction in the transcriptional activity of the chglast promoter through the Ca 2+ /diacylglicerol‐dependent protein kinase (PKC) signaling cascade. Overexpression of constitutive active PKC isoforms of mimic the glutamate effect. Accordingly, increased levels of c‐Jun or c‐Fos, but not Jun‐B, Jun‐D or Fos‐B, lower the chglast promoter activity. Serial deletions and electrophorectic mobility shift assays were used to define a specific region within the 5′ proximal region of the chglast promoter, associated with transcriptional repression. A putative glutamate response element could be defined in the proximal promoter stretch more likely between nts – 40 and − 78. These results demonstrate that GLAST is under glutamate‐dependent transcriptional control through PKC, and support the notion of a pivotal role of this neurotransmitter in the regulation of its own removal from the synaptic cleft, thereby modulating, mainly in the long term, glutamatergic transmission.