Figure 9
Simplified model of the novel function of DREAM in NMDA receptor-mediated signaling transduction at synapses. At postsynaptic sites, DREAM interacts with PSD-95, and inhibits the functions of NMDA receptors. Binding of Ca2+ to DREAM releases the interaction between DREAM and PSD95. In TgDREAM mice, Ca2+-insensitive mutant DREAM may constitutively bind to PSD95, leading to the impaired recruitment of PSD-95 and reduced NMDA receptor function. The loss of LTD in TgDREAM mice is likely due to the impaired function of NMDA receptors. Within the nucleus, it is known that DREAM binds to DRE located downstream from the transcriptional start site, and inhibits the promoter activity. The binding of Ca2+ to DREAM releases this inhibition, leading to higher levels of transcription.