The effect of ER stress on activity-dependent induction of brain-derived neurotrophic factor exon III

Neuronal activity promotes neuronal survival and increases synaptic strength. These effects are primarily mediated by influx of calcium through L-type calcium channels during membrane depolarization. This activates the transcription factor CREB by phosphorylating it on Ser-133 and induces several genes including BDNF exon III that play important roles in activity-dependent neuronal survival. Since ER stress is known to perturb intracellular calcium signaling, we examined whether it attenuated depolarization-induced CREB Ser-133 phosphorylation and BDNF exon III expression in PC12 cells. ER stress induced by tunicamycin, beta-mercaptoethanol, or thapsigargin did not reduce depolarization-induced CREB Ser-133 phosphorylation. However it did suppress the induction of BDNF exon III by membrane depolarization, indicating that it exerts this effect by blocking a pathway distinct from CREB Ser-133 phosphorylation.