Figure 1.

Possible mechanisms of DREAM action. (1) High [Ca²⁺] levels inhibits the transcriptional activity of DREAM; (2) DREAM participates in the plasma membrane trafficking of the Kv4.2 potassium channel; (3) DREAM sumoylation allows entering into the nucleus to exert as transcription and/or epigenetic factor; (4) DREAM regulates the transcription of proteins involved in the maintenance of Ca²⁺ homeostasis; (5) DREAM regulates the activity of NMDA receptors by directly inhibiting the NR1 subunit; (6) DREAM participates in the regulation of presenilin 2 activity; (7) DREAM, upon low levels of [Ca²⁺], directly binds to CREB and prevents its phosphorylation and thus its transcriptional activity. Abbreviations: APP, amyloid precursor protein; NMDA-R, N-methyl-D-aspartate receptor; PS-2, presenilin-2; NCX3, Na⁺/Ca²⁺ exchanger 3; GFAP, Glial fibrillary acidic protein.