title: Signaling through EAAT-1/GLAST in cultured Bergmann glia cells.
abstract: Glutamate, the major excitatory amino acid, activates a wide variety of signal transduction cascades. Synaptic plasticity relies on activity-dependent differential protein expression. Ionotropic and metabotropic glutamate receptors have been critically involved in long-term synaptic changes, although recent findings suggest that the electrogenic Na(+)-dependent glutamate transporters, responsible of its removal from the synaptic cleft, participate in glutamate-induced signaling. Transporter proteins are expressed in neurons and glia cells albeit most of the glutamate uptake occurs in the glial compartment. Within the cerebellum, Bergmann glial cells are close to glutamatergic synapses and participate actively in the recycling of glutamate through the glutamate/glutamine shuttle. In this context, we decided to investigate a plausible role of Bergmann glia glutamate transporters as signaling entities. To this end, primary cultures of chick cerebellar Bergmann glial cells were exposed to d-aspartate (D-Asp) and other transporter ligands and the serine 2448 phosphorylation pattern of the master regulator of protein synthesis, namely the mammalian target of rapamycin (mTOR), determined. An increase in mTOR phosphorylation and activity was detected. The signaling cascade included Ca(2+) influx, activation of the phosphatidylinositol 3-kinase and protein kinase B. Furthermore, transporter signaling resulted also in an increase in activator protein-1 (AP-1) binding to DNA and the up-regulation of the transcription of an AP-1 driven gene construct. These results add a novel mediator of the glutamate effects at the translational and transcriptional levels and further strengthen the notion of the critical involvement of glia cells in synaptic function.
authors.affiliation: Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, México DF 07000, Mexico.
authors.forename: Zila
authors.initials: Z
authors.lastname: Martínez-Lozada
authors.forename: Luisa C
authors.initials: LC
authors.lastname: Hernández-Kelly
authors.forename: José
authors.initials: J
authors.lastname: Aguilera
authors.forename: Esther
authors.initials: E
authors.lastname: López-Bayghen
authors.forename: Arturo
authors.initials: A
authors.lastname: Ortega
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent; D002642:Chick Embryo; D002645:Chickens; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D009457:Neuroglia / Q000145:classification* / Q000201:enzymology / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D001224:Aspartic Acid; D002118:Calcium; D002413:Cations, Divalent; D027341:Excitatory Amino Acid Transporter 1; D018698:Glutamic Acid; D058539:Phosphatidylinositol 3-Kinase; D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases