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The Secretogranin II Gene Is a Signal Integrator of Glutamate and Dopamine Inputs

Iwase, Katsuro
Ishihara, Akinori
Yoshimura, Shuntaro
Andoh, Yoshio
Kato, Masaki
Seki, Naohiko
Matsumoto, Eriko
Hiwasa, Takaki
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Published in Journal of Neurochemistry. 2014, vol. 128, no. 2, p. 233-245
Abstract Cooperative gene regulation by different neurotransmitters likely underlies the long-term forms of associative learning and memory, but this mechanism largely remains to be elucidated. Following cDNA microarray analysis for genes regulated by Ca(2+) or cAMP, we found that the secretogranin II gene (Scg2) was cooperatively activated by glutamate and dopamine in primary cultured mouse hippocampal neurons. The Ca(2+) chelator BAPTA-AM and the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 prevented Scg2 activation by glutamate or dopamine; thus, the Ca(2+) /MEK pathway is predicted to include a convergence point(s) of glutamatergic and dopaminergic signaling. Unexpectedly, the protein kinase A (PKA) inhibitor KT5720 enhanced Scg2 activation by dopamine. The protein-synthesis inhibitor cycloheximide also enhanced Scg2 activation, and the proteasome inhibitor ZLLLH diminished the KT5720-mediated augmentation of Scg2 activation. These results are concordant with the notion that dopaminergic input leads to accumulation of a KT5720-sensitive transcriptional repressor, which is short-lived because of rapid degradation by proteasomes. This repression pathway may effectively limit the time window permissive to Scg2 activation by in-phase glutamate and dopamine inputs via the Ca(2+) /MEK pathway. We propose that the regulatory system of Scg2 expression is equipped with machinery that is refined for the signal integration of in-phase synaptic inputs. This article is protected by copyright. All rights reserved.
PMID: 24111984
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Research group Plasticité des synapses excitatrices (76)
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IWASE, Katsuro et al. The Secretogranin II Gene Is a Signal Integrator of Glutamate and Dopamine Inputs. In: Journal of Neurochemistry, 2014, vol. 128, n° 2, p. 233-245. https://archive-ouverte.unige.ch/unige:33927

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Deposited on : 2014-01-31

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