Egr-1 modulation of synapsin I expression: permissive effect of forskolin via cAMP

James, A.B. , Conway, A.M., Thiel, G. and Morris, B.J. (2004) Egr-1 modulation of synapsin I expression: permissive effect of forskolin via cAMP. Cellular Signalling, 16, pp. 1355-1362. (doi: 10.1016/j.cellsig.2004.04.001)

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A number of candidate Egr-1 neuronal target genes have been identified including the synapsin I gene. Previous studies have shown that over-expression of Egr-1 in cells transfected with an Egr-1 expression vector is sufficient to activate reporter genes linked to regions of the synapsin I promoter, but any effect on the expression of synapsin I within its genomic context has not been demonstrated. We tested our hypothesis that modulation of synapsin I expression by Egr-1 requires the presence of elevated cAMP which would normally be present during periods of neuronal plasticity. Both the adenyl cyclase activator, forskolin (frsk), and the cAMP analogue, Sp-Adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt (Sp-cAMPS), enhanced the ability of Egr-1 to transactivate a CAT reporter plasmid containing multiple copies of the Egr-1 binding site (EBS). Furthermore, Egr-1 alone had minimal effects on synapsin I expression whereas forskolin treatment of PC12 cells profoundly affected the ability of Egr-1 to regulate synapsin I expression. These results suggest that Egr-1 transactivation during neuronal plasticity may rely on a permissive effect of cAMP.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Morris, Professor Brian and James, Dr Allan
Authors: James, A.B., Conway, A.M., Thiel, G., and Morris, B.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Cellular Signalling
ISSN (Online):1873-3913
Published Online:01 January 2004

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