TY - JOUR
T1 - Transcriptional regulation of neuronal genes and its effect on neural functions
T2 - Cumulative mRNA expression of PACAP and BDNF genes controlled by calcium and cAMP signals in neurons
AU - Fukuchi, Mamoru
AU - Tabuchi, Akiko
AU - Tsuda, Masaaki
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
KW - Brain-derived neurotrophic factor
KW - Calcium
KW - Pituitary adenylate cyclase-activating polypeptide
KW - Transcription
KW - mRNA degradation
UR - http://www.scopus.com/inward/record.url?scp=24744460302&partnerID=8YFLogxK
U2 - 10.1254/jphs.FMJ05001X4
DO - 10.1254/jphs.FMJ05001X4
M3 - 学術論文
C2 - 16006741
AN - SCOPUS:24744460302
SN - 1347-8613
VL - 98
SP - 212
EP - 218
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
IS - 3
ER -