Transcriptional regulation by cAMP and Ca2+ links the Na/Ca2+ exchanger 3 to memory and sensory pathways

The signaling cascades triggered by neurotrophins such as BDNF and by several neurotransmitters and hormones lead to the rapid induction of gene transcription by increasing the intracellular concentration of cAMP and Ca2+. This review examines the mechanisms by which these second messengers control transcriptional initiation at CRE promoters via transcription factor CREB, as well as at DRE sites via transcriptional repressor DREAM. The regulation of the SLC8A3 gene encoding the Na+/Ca2+ exchanger 3 (NCX3) is taken as an example to illustrate both mechanisms since it includes a CRE site in the promoter and several DRE sites in the exon 1 sequence. The upregulation of the NCX3 by Ca2+ signals may be specifically required to establish the Ca2+ balance that regulates several physiological and pathological processes in neurons. The regulatory features and the expression pattern of SLC8A3 gene suggest that NCX3 activity could be crucial in neuronal functions such as memory formation and sensory processing.