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Glutamate-Dependent Translational Control of Glutamine Synthetase in Bergmann Glia Cells

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Abstract

Glutamate is the major excitatory transmitter of the vertebrate brain. It exerts its actions through the activation of specific plasma membrane receptors expressed both in neurons and in glial cells. Recent evidence has shown that glutamate uptake systems, particularly enriched in glia cells, trigger biochemical cascades in a similar fashion as receptors. A tight regulation of glutamate extracellular levels prevents neuronal overstimulation and cell death, and it is critically involved in glutamate turnover. Glial glutamate transporters are responsible of the majority of the brain glutamate uptake activity. Once internalized, this excitatory amino acid is rapidly metabolized to glutamine via the astrocyte-enriched enzyme glutamine synthetase. A coupling between glutamate uptake and glutamine synthesis and release has been commonly known as the glutamate/glutamine shuttle. Taking advantage of the established model of cultured Bergmann glia cells, in this contribution, we explored the gene expression regulation of glutamine synthetase. A time- and dose-dependent regulation of glutamine synthetase protein and activity levels was found. Moreover, glutamate exposure resulted in the transient shift of glutamine synthetase mRNA from the monosomal to the polysomal fraction. These results demonstrate a novel mode of glutamate-dependent glutamine synthetase regulation and strengthen the notion of an exquisite glia neuronal interaction in glutamatergic synapses.

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Acknowledgements

RTF and DM are supported by CONACyT Mexico scholarships. This work was funded by CONACyT, Mexico (255087), and Soluciones para un México Verde, S.A. de C.V. grants to AO.

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Authors and Affiliations

  1. Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN, Apartado Postal 14-740, 07360, Ciudad de México, Mexico

    Reynaldo Tiburcio-Félix, Daniel Martínez & Samuel Zinker

  2. Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN, Apartado Postal 14-740, 07360, Ciudad de México, Mexico

    Miguel Escalante-López, Bruno López-Bayghen, Luisa C. Hernández-Kelly, Dinorah Hernández-Melchor, Esther López-Bayghen & Arturo Ortega

  3. Instituto de Investigaciones Oceanológicas, Universidad Autónoma de Baja California, 22860, Ensenada, Mexico

    Tatiana N. Olivares-Bañuelos

Authors
  1. Reynaldo Tiburcio-Félix
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  2. Miguel Escalante-López
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  3. Bruno López-Bayghen
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  4. Daniel Martínez
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  5. Luisa C. Hernández-Kelly
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  6. Samuel Zinker
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  7. Dinorah Hernández-Melchor
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  8. Esther López-Bayghen
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  9. Tatiana N. Olivares-Bañuelos
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  10. Arturo Ortega
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Correspondence to Arturo Ortega.

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All efforts were made to reduce the number of embryos used and their suffering according to International Guidelines on the Ethical Use of Animals.

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Tiburcio-Félix, R., Escalante-López, M., López-Bayghen, B. et al. Glutamate-Dependent Translational Control of Glutamine Synthetase in Bergmann Glia Cells. Mol Neurobiol 55, 5202–5209 (2018). https://doi.org/10.1007/s12035-017-0756-3

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  • DOI: https://doi.org/10.1007/s12035-017-0756-3

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