Glutamate-dependent elongation factor-2 phosphorylation in Bergmann glial cells.

Glutamate, the main excitatory amino acid transmitter regulates protein biosynthesis at the transcriptional and translational levels. It is critically involved in the continuous change of the protein repertoire that is inherent to synaptic plasticity. Activity-dependent differential gene expression occurs both in neurons and glial cells. In fact, besides a membrane to nuclei signaling that leads to transcriptional control, a biphasic effect in overall protein synthesis takes place after glutamate receptors stimulation in cultured chick cerebellar Bergmann glia. Therefore, the effect of glutamate receptors activation on translation elongation was characterized. A time- and dose-dependent increase in eukaryotic elongation factor-2 phosphorylation was found. Pharmacological tools established that alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and Kainate, but not N-methyl-d-aspartate trigger this phosphorylation. The removal of external Ca2+ or the pre-treatment with a calmodulin antagonist prevented the glutamate effect. Accordingly, glutamate receptors regulate eukaryotic elongation factor-2 kinase phosphorylation through the involvement of Ca2+/calmodulin/extracellular-regulated protein kinases 1/2. These results demonstrate that glutamate receptors regulate the elongation of peptide chains in glial cells.