Glutamate regulates eEF1A phosphorylation and ribosomal transit time in Bergmann glial cells.
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.
Barrera
Iliana
I
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México DF, Mexico.
Flores-Méndez
Marco
M
Hernández-Kelly
Luisa C
LC
Cid
Luis
L
Huerta
Miriam
M
Zinker
Samuel
S
López-Bayghen
Esther
E
Aguilera
José
J
Ortega
Arturo
A
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
C094814:EEF1A1 protein, human; D020648:Peptide Elongation Factor 1; D017470:Receptors, Glutamate; D013912:Threonine; D018698:Glutamic Acid