Ionotropic glutamate receptors in cerebellar Bergmann glial cells are linked to transcriptional regulation and, by these means, are thought to play an important role in plasticity, learning and memory and in several neuropathologies. Within the CNS, the transcription factors of the POU family bind their target DNA sequences after a growth factordependent phosphorylation-dephosphorylation cascade. Exposure of cultured Bergmann glial cells to glutamate leads to a time-and dose-dependent increase in Oct-2 DNAbinding activity. The use of specific pharmacological tools established the involvement of Ca 2+ -permeable a-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors. Furthermore, the signaling cascade includes phosphatidyl inositol 3-kinase as well as protein kinase C activation. Interestingly, transcriptional as well as translational inhibitors abolish the glutamate effect, suggesting a transcriptional up-regulation of the oct-2 gene. These data demonstrate that Oct-2 expression is not restricted to neurons and further strengthen the notion that the glial glutamate receptors participate in the modulation of glutamatergic cerebellar neurotransmission.

Glutamate, the major excitatory neurotransmitter, induces a wide array of signals from the membrane to the nucleus regulating gene expression. In Bergmann glia, Ca2+ -permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid (AMPA) receptors are involved in the short- and long-term interactions between these cells and the neurons that they surround. After activation, AMPA receptors become tyrosine phosphorylated and by these means form multiprotein signaling complexes. To characterize these events, cultured chick Bergmann glia cells as well as chick cerebellar slices were exposed to glutamate, and, by using a combination of immunoprecipitation assays coupled to Western blot analysis, we identified several signaling proteins that become associated with these receptors. A dose- and time-dependent association among AMPA receptors, the focal adhesion kinase pp125FAK, the phosphatidylinositol-3 kinase and paxillin was found. These results extend the concept of the transducisome to AMPA receptors and provide a framework in which a plausible control of the cytoskeletal network by glutamate is taking place, most possibly through AMPA receptors.

Glial glutamate receptors are likely to play a role in plasticity, learning, and memory and in a number of neuropathologies. An enhanced glutamate-dependent tyrosine phosphorylation has been detected in such processes. Using primary cultures of chick Bergmann glia cells and chick cerebellar slices, we addressed whether glial glutamate receptors can activate the nonreceptor tyrosine kinase pp125 focal adhesion kinase (pp125(FAK)). A dose- and time-dependent tyrosine phosphorylation of pp125(FAK) was found in both preparations upon glutamate treatment. This effect was mediated through alpha-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate (AMPA)/kainate (KA) receptors, as shown by its inhibition by the specific antagonists 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7- sulfonamide (NBQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) and the lack of effect of metabotropic agonists. FAK tyrosine phosphorylation was dependent on phosphatidylinositol 3-kinase activity. As expected, an increase in pp125(FAK) catalytic activity was found upon glutamate treatment. Immunprecipitation experiments demonstrated that FAK associates with ionotropic glutamate receptors. Taken together, these results suggest a role for glial glutamate receptors in cytoskeletal rearrengments and focal adhesion contact formation and provide new insight into the signaling transactions elicited by this neurotransmitter in glial cells.