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

Journal of Pharmacological Sciences

Masaaki Tsuda¹  Akiko Tabuchi¹  Mamoru Fukuchi¹ 

[1] Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University

关键词: brain-derived neurotrophic factor;    pituitary adenylate cyclase-activating polypeptide;    calcium;    transcription;    mRNA degradation;   

DOI  :  10.1254/jphs.FMJ05001X4

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(22)Cited-By(18)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.

【 授权许可】

Unknown