Wnt signaling induces GLT-1 expression in rat C6 glioma cells.

The regulation of glial and neuronal Na+-dependent glutamate/aspartate transporters is of interest because abnormal glutamate transport may be responsible for certain neurological diseases. Because expression of the Wnt-1 protooncogene results in induction of the glial-type glutamate transporter GLAST in PC12 neuron-like cells, we have evaluated the effect of Wnt-1-induced signaling on glutamate transporter expression in rat C6 glioma cells. C6 cells are known normally to express EAAC1, a neuronal glutamate transporter, but not the GLAST or the GLT-1 glutamate transporter. C6 cells that ectopically expressed Wnt-1 contained a GLT-1 RNA species similar in size (>10 kb) to the GLT-1 transcript present in rat brain, and they also contained a previously unreported 3.3-kb GLT-1 RNA species. Both GLT-1 RNAs contain large parts of the coding region. However, the 3.3-kb GLT-1 species contains at least one small deletion within the coding region. The Wnt-1-expressing C6 cells contained little, if any, GLT-1 protein as determined by immunological techniques. We suggest that one or both of the GLT-1 RNA species induced by Wnt-1 either fail to be translated or yield abnormal translation products that are quickly degraded. Wnt-1-expressing C6 cells may thus represent a novel in vitro system for studying GLT-1 transporter expression at the transcriptional and/or posttranscriptional levels.