Glutamate-dependent transcriptional control in Bergmann glia: Sox10 as a repressor.

UNLABELLED: 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. KEYWORDS: Bergmann glial cells, glutamate, metabotropic glutamate receptors, signaling, Sox10, transcriptional control.