Glutamate-dependent translational control through ribosomal protein S6 phosphorylation in cultured bergmann glial cells.
Glutamate (Glu) the main excitatory neurotransmitter of the central nervous system regulates gene expression at different levels through the activation of specific membrane receptors and transporters expressed in neurons and glia cells. A membrane to nucleus signaling cascade triggered by this neurotransmitter has been described in cultured cerebellar Bergmann glia cells isolated from chick embryos. Furthermore, it has also been described that Glu receptors activation is linked to a modulation of [(35)S]-methionine incorporation into newly synthesized polypeptides. In order to gain insight into the signal transduction cascades that participate in this effect, in the present study we characterized the phosphorylation of a critical component of the translational machinery, namely the ribosomal protein S6. The phosphorylation sites in rpS6 have been mapped to five clustered residues, Ser235, Ser236, Ser240, Ser244 and Ser247. Nevertheless, Ser236 phosphorylation is the primary phosphorylation site. The kinases responsible of this modification are p70(S6K) and p90(RSK). rpS6 phosphorylation increases the affinity of 40s subunit for mRNAs and thus facilitates translational initiation. Glutamate exposure of cultured cerebellar Bergmann glia cells results in a time- and dose-dependent increase in rpS6 phosphorylation. This effect is mainly observed at cytoplasm, and involves the phosphoinositol-3 kinase/protein kinase B pathway. Our results favor the notion of a continuous neuronal signaling to glia cells that regulates the proteome of these cells not only at the transcriptional level but also at the level of protein synthesis.
Laboratorio de Neurotoxicología, Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, 07300, Mexico, D.F., Mexico.
Marco
M
Flores-Méndez
Miguel
M
Escalante-López
Zila
Z
Martínez-Lozada
Luisa C
LC
Hernández-Kelly
Mustapha
M
Najimi
Etienne
E
Sokal
Arturo
A
Ortega
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000502:physiology*; D038601:Ribosomal Protein S6 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D038601:Ribosomal Protein S6; D018698:Glutamic Acid