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
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概要
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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 Ca2+ 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 Ca2+ and cAMP signals not only at the transcriptional level but also at the post-transcriptional level for the cumulative mRNA expression in neurons.
- 社団法人 日本薬理学会の論文
- 2005-07-20
著者
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TSUDA Masaaki
Department of Microbiology, Faculty of Pharmaceutical Sciences, Okayama University
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Tsuda Masaaki
Department Of Biological Chemistry Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceuti
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Tsuda Masaaki
Depertment Of Biological Chemistry Faculty Of Pharmcetutical Science Toyama Medical And Pharmaceutic
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FUKUCHI Mamoru
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceu
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TABUCHI Akiko
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceu
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Tabuchi Akiko
University Of Toyama Department Of Biological Chemistry Graduate School Of Medicine And Pharmaceutic
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Fukuchi Mamoru
University Of Toyama Department Of Biological Chemistry Graduate School Of Medicine And Pharmaceutic
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