title: Glutamate regulates eEF1A phosphorylation and ribosomal transit time in Bergmann glial cells.
abstract: Glutamate, the major excitatory transmitter in the vertebrate brain, is involved in neuronal development and synaptic plasticity. Glutamatergic stimulation leads to differential gene expression patterns in neuronal and glial cells. A glutamate-dependent transcriptional control has been established for several genes. However, much less is known about the molecular events that modify the translational machinery upon exposure to this neurotransmitter. In a glial model of cerebellar cultured Bergmann cells, glutamate induces a biphasic effect on [(35)S]-methionine incorporation into proteins that suggests that the elongation phase of protein biosynthesis is the target for regulation. Indeed, after a 15 min exposure to glutamate a transient increase in elongation factor 2 phosphorylation has been reported, an effect mediated through the activation of the elongation factor 2 kinase. In this contribution, we sought to characterize the phosphorylation status of the eukaryotic elongation factor 1A (eEF1A) and the ribosomal transit time under glutamate exposure. A dose-dependent increase in eEF1A phosphorylation was found after a 60 min glutamate treatment; this phenomenon is Ca(2+)/CaM dependent, blocked with Src and phosphatidyl-inositol 3-kinase inhibitors and with rapamicyn. Concomitantly, the ribosomal transit time was increased with a 15 min glutamate exposure. After 60 more minutes, the average time used by the ribosomes to complete a polypeptide chain had almost returned to its initial level. These results strongly suggest that glutamate exerts an exquisite time-dependent translational control in glial cells, a process that might be critical for glia-neuron interactions.
authors.affiliation: Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México DF, Mexico.
authors.forename: Iliana
authors.initials: I
authors.lastname: Barrera
authors.forename: Marco
authors.initials: M
authors.lastname: Flores-Méndez
authors.forename: Luisa C
authors.initials: LC
authors.lastname: Hernández-Kelly
authors.forename: Luis
authors.initials: L
authors.lastname: Cid
authors.forename: Miriam
authors.initials: M
authors.lastname: Huerta
authors.forename: Samuel
authors.initials: S
authors.lastname: Zinker
authors.forename: Esther
authors.initials: E
authors.lastname: López-Bayghen
authors.forename: José
authors.initials: J
authors.lastname: Aguilera
authors.forename: Arturo
authors.initials: A
authors.lastname: Ortega
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism*; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D014176:Protein Biosynthesis; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D017470:Receptors, Glutamate / Q000502:physiology; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013912:Threonine / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: C094814:EEF1A1 protein, human; D020648:Peptide Elongation Factor 1; D017470:Receptors, Glutamate; D013912:Threonine; D018698:Glutamic Acid