Journal
NEUROCHEMICAL RESEARCH
Volume 38, Issue 7, Pages 1324-1332Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-013-1024-1
Keywords
Bergmann glia; Eukaryotic initiation factor 2; Glutamate receptors; Translational control
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Funding
- Conacyt-Mexico [79502, 123625]
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Glutamate (Glu), the major excitatory amino acid, activates a wide variety of signal transduction cascades. Synaptic plasticity relies on activity-dependent differential protein expression. Glu receptors have been critically involved in long-term synaptic changes, although recent findings suggest that Na+-dependent Glu transporters participate in Glu-induced signalling. Within the cerebellum, Bergmann glia cells are in close proximity to glutamatergic synapses and through their receptors and transporters, sense and respond to neuronal glutamatergic activity. Translational control represents the fine-tuning stage of protein expression regulation and Glu modulates this event in glial cells. In this context, we decided to explore the involvement of Glu receptors and transporters in the regulation of the initiation phase of protein synthesis. To this end, Bergmann glia cells were exposed to glutamatergic ligands and the serine 51-phosphorylation pattern of the main regulator of the initiation phase of translation, namely the alpha subunit of eukaryotic initiation factor 2 (eIF2 alpha), determined. A time and dose-dependent increase in eIF2 alpha phosphorylation was detected. The signalling cascade included Ca2+ influx, activation of the Ca2+/calmodulin-dependent protein kinase II and protein kinase C. These results provide an insight into the molecular targets of the Glu effects at the translational level and strengthen the notion of the critical involvement of glia cells in glutamatergic synaptic function.
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