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Control of the Na + /Ca 2+ exchanger 3 promoter by cyclic adenosine monophosphate and Ca 2+ in differentiating neurons
Author(s) -
Gabellini Nadia,
Bortoluzzi Stefania,
Danieli Gian A.,
Carafoli Ernesto
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01511.x
Subject(s) - microbiology and biotechnology , retinoic acid , protein kinase a , creb , phosphorylation , biology , cyclic adenosine monophosphate , chemistry , transcription factor , biochemistry , gene , receptor
The human gene for member 3 of solute carrier family 8 (SLC8A3), encoding the Na + /Ca 2+ exchanger isoform 3 (NCX3), was identified on chromosome 14q24.2. The minimal promoter region was predicted 250 bp upstream of exon 1. This was confirmed by luciferase reporter assays of pGL3‐promoter constructs in transfected SH‐SY5Y cells. The promoter activity was monitored during the differentiation of this cell line elicited by the sequential treatment with retinoic acid and brain‐derived neurotrophic factor (BDNF). The activity was induced by cyclic AMP (cAMP) via the CRE (cAMP response element) and was stimulated by retinoic acid. The increase of intracellular Ca 2+ induced by the partial depolarization of the plasma membrane with KCl down‐regulated both the basal and the cAMP‐stimulated transcription. The down‐regulation of the latter may be mediated by the phosphorylation of the CRE‐binding protein by a calmodulin‐dependent kinase (CaMKII). The exposure of cells to BDNF after treatment with retinoic acid rapidly induced promoter activity during the initial five hours and phosphorylation of CRE‐binding protein during the first two hours. The promoter activity was further enhanced by cAMP, but became insensitive to Ca 2+ . In BDNF‐stimulated cells cAMP elevation caused the preferential phosphorylation of ATF1 instead of that of CRE‐binding protein.