Glutamate-dependent transcriptional regulation of GLAST/EAAT1: a role for YY1
Article first published online: 26 FEB 2007
Journal of Neurochemistry
Volume 101, Issue 4, pages 1134–1144, May 2007
How to Cite
Rosas, S., Vargas, M. A., López-Bayghen, E. and Ortega, A. (2007), Glutamate-dependent transcriptional regulation of GLAST/EAAT1: a role for YY1. Journal of Neurochemistry, 101: 1134–1144. doi: 10.1111/j.1471-4159.2007.04517.x
- Issue published online: 26 FEB 2007
- Article first published online: 26 FEB 2007
- Received September 28, 2006; revised manuscript received December 4, 2006; accepted December 4, 2006.
- glutamate receptors;
- transcriptional control;
- Bergmann glia;
Glutamate is the major excitatory transmitter in the vertebrate brain and its extracellular levels are tightly regulated to prevent excitotoxic effects. The Na+-dependent glutamate/aspartate transporter GLAST/EAAT1 is regulated in the short and in the long term by glutamate. A receptors-independent change in its membrane translocation rate, accounts for an acute modulation in GLAST/EAAT1 transport. In contrast, activation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionate subtype of glutamate receptors represses the transcription of the chick glast gene. A glutamate responsive element has been mapped to the promoter region of this gene containing a bonafide binding site for the transcription factor Ying-Yang 1. Using cultured chick cerebellar Bergmann glia cells, glutamate elicited a time and dose-dependent increase in Ying-Yang 1 DNA binding consistent with the negative response generated in a reporter gene construct controlled for Ying-Yang 1. Over-expression of this transcription factor leads to a substantial reduction in GLAST/EAAT1 transporter uptake and an important decrease in mRNA levels, all associated with the transcriptional repression of the chick glast promoter activity. These results provide evidence for an involvement of Ying-Yang 1 in the transcriptional response to glutamate in glial cells and favor the notion of a relevant role of this factor in GLAST/EAAT1 transcriptional control.