Glutamate, the main excitatory neurotransmitter in the vertebrate brain, is critically involved in gene expression regulation in neurons and in glia cells. Neuron-glia interactions provide the framework for synaptic plasticity. Retinal and cerebellar radial glia cells surround glutamatergic excitatory synapses and sense synaptic activity through glutamate receptors expressed in their membranes. Several glutamatedependent membrane to nuclei signaling cascades have been described in these cells. Octamer DNA binding factors, namely Oct-1 and Oct-2 recognize similar DNA sequences on regulatory regions, but their final transcriptional effect depends on several factors. By these means, different responses can be achieved in different cell types. Here, we describe a comparison between the glutamate-induced DNA binding of octamer factors and their functional activities in two important types of radial glia, retinal Mü ller and cerebellar Bergmann glial cells. While Oct-1 is expressed in both cell types and in both glutamate treatments results in an increase in Oct-1 DNA binding, this complex is capable of transactivating a reporter gene only in Mü ller glia cells. In contrast, Oct-2 expression is restricted to Bergmann glia cells in which glutamate treatment results in an augmentation of Oct-2 DNA binding complexes and the repression of kainate binding protein gene transcription. Our present findings demonstrate a differential role for Oct-1 and Oct-2 transcription factors in glial glutamate signaling, and further strengthen the notion of an important role for glial cells in glutamatergic transactions in the central nervous system.
J. Neurochem. (2009) 109, 899–910. Abstract Glutamate (Glu) is the major excitatory transmitter in the vertebrate brain. Ligand‐gated and G protein‐coupled Glu receptors present in glial cells are presumably involved in neuronal function. Activation of Bergmann glial Glu receptors triggers a membrane to nuclei signaling cascade that regulates gene expression at the transcriptional and translational levels. Sry‐related high‐mobility group box (Sox10), a member of the conserved high‐mobility group box transcription factor family is expressed in neural crest stem cells and in a subset of neural crest‐derived lineages that include glial, but not neuronal cells. To gain insight into the role of Sox10 in Bergmann glial cells, we explored its expression and regulation. We demonstrate herein that Sox10 is expressed in Bergmann glial cells and that its DNA binding activity, mRNA, and protein levels as well as its transcriptional behavior augments upon the activation of metabotropic Glu receptors. Increase in Sox10–DNA complexes and Sox10 mRNA and protein levels were found upon exposure to Glu. Over‐expression of Sox10 leads to transcriptional repression in reporter gene assays and in one of its target genes: the chick kainate binding protein gene. These findings add a new perspective into glial glutamatergic signaling and suggest the participation of Sox10 in cerebellar glutamatergic transactions.
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