Transcriptional regulation of neuronal genes and its effect on neural functions: Cumulative mRNA expression of PACAP and BDNF genes controlled by calcium and cAMP signals in neurons

Mamoru Fukuchi, Akiko Tabuchi, Masaaki Tsuda*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

47 被引用数 (Scopus)

抄録

Although it is widely accepted that an activity-dependent gene transcription is induced by the calcium (Ca2+) signals in neurons, it is still unclear how the particular mRNA moieties are transiently accumulated in response to synaptic transmission that evokes multiple intracellular signals including Ca2+ and cAMP ones. Promoters of the brain-derived neurotrophic factor (BDNF) and the pituitary adenylate cyclase-ativating polypeptide (PACAP) can commonly be activated through the cAMP-responsive element (CRE), to which the CRE-binding protein (CREB) predominantly bound. The activation of BDNF gene promoter I and III (BDNF-PI and -PIII, respectively) was mediated not only by the CREB but also by the upstream stimulatory factor, whereas that of PACAP gene promoter (PACAP-P) was mediated by only one CRE located at around -200. The PACAP-P was synergistically enhanced by Ca 2+ and cAMP signals through the CRE, whereas the BDNF-PI did not show such a synergistic activation upon the stimulation with both signals. In addition, we found that the half-lives of PACAP and BDNF mRNA were prolonged by the Ca2+ influx into neurons but not that of Arc mRNA, indicating an activity-dependent stabilization of particular mRNA species in neurons. Thus, the activity-dependent gene expression is co-ordinately controlled by Ca 2+ and cAMP signals not only at the transcriptional level but also at the post-transcriptional level for the cumulative mRNA expression in neurons.

本文言語英語
ページ(範囲)212-218
ページ数7
ジャーナルJournal of Pharmacological Sciences
98
3
DOI
出版ステータス出版済み - 2005

ASJC Scopus 主題領域

  • 分子医療
  • 薬理学

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