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Biochim Biophys Acta. 1995 Apr 4;1261(2):249-56.

The CRE consensus sequence in the synapsin I gene promoter region confers constitutive activation but no regulation by cAMP in neuroblastoma cells.

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Institut für Physiologische Chemie, Medizinische Fakultät, Ruhr-Universität Bochum, Germany.


Synapsin I is implicated in the modulation of neurotransmitter release and in synaptogenesis and is regulated by phosphorylation. The rat and human synapsin I genes both carry CRE and TRE consensus sequences in their promoter regions. This suggested that protein kinase-mediated signal pathways might also regulate synapsin I activity at the level of gene expression and thus contribute, on a slower time scale, to synaptic plasticity. We have therefore investigated, in neuroblastoma cell lines, the effects of agents that activate protein kinases on synapsin I gene expression. Unexpectedly, treatment with forskolin/IBMX was not found to enhance synapsin I mRNA levels. Rather, it causes a decrease to approximately 50% within 1 day although several CRE-dependent control genes are strongly induced. The calcium ionophore, A23187, lowers synapsin I mRNA to approximately 75%, and the phorbol ester, TPA, is without effect. Transient expression of a CAT fusion gene under the control of the synapsin I promoter region is also inhibited by forskolin/IBMX, as well as by protein kinase A (PKA) overexpression, suggesting that the decrease of synapsin I mRNA in response to forskolin/IBMX is due to the inhibition of transcription. Mutation of the CRE consensus does not affect the response to PKA, but it reduces the constitutive activity of synapsin I promoter constructs down to 30-50%. Nuclease footprinting experiments demonstrate sequence-specific binding proteins from brain, liver and NS20Y cell nuclear extracts to the CRE consensus sequence of the rat synapsin I promoter.

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