Regulation of gene expression involved in conveying information between synapses and nuclei in neurons
| Project/Area Number |
20390023
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | University of Toyama |
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Principal Investigator |
MASAAKI Tsuda University of Toyama, 大学院・医学薬学研究部(薬学), 教授 (80132736)
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| Co-Investigator(Kenkyū-buntansha) |
AKIKO Tabuchi 富山大学, 大学院・医学薬学研究部(薬学), 准教授 (40303234)
MAMORU Fukuchi 富山大学, 大学院・医学薬学研究部(薬学), 助教 (40432108)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2009: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | 遺伝子発現 / シナプス / BDNF / PACAP / CREB / MKL / GPCR / Arc / MAL/MKL / TORC / カルシウム / MAL / アクチン / SRF |
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| Research Abstract |
Since G protein-coupled receptors (GPCRs) potentiate the activity of the N-methyl-D-aspartate receptor (NMDA-R), we comprehensively investigated gene expression induced by the stimulation of GPCRs in culture. Potentiation of NMDA-R mediated by the activation of PAC1, a GPCR, with PACAP immediately activated a limited number of genes upon Ca^<2+> signals. The mRNA expression of the brain-derived neurotrophic factor exon IV-IX (Bdnf-eIV) is totally controlled by Ca^<2+>/calcineurin, leading to the CRE/CREB-dependent transcription. Stimulation of NMDA-R under the activation of PAC1 synergistically increased Bdnf-eIV mRNA expression through the selective activation of calcineurin, leading to translocation of TORC1 to nucleus and activation of CREB-KID domain. The Ca^<2+>/calcineurin-dependent mRNA expression was also induced by direct stimulation of PKA or PKC pathway and, furthermore, by that of the dopamine D1 or β-adrenergic receptor. Thus, the potentiation of NMDA-R activity mediated by GPCR induces activity-dependent gene expression through calcineurin pathway, possibly regardless of the type of neurotransmission.
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Report
(4 results)
Research Products
(71 results)
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[Journal Article] Antibody to varicella-zoster virus immediate-early protein 62 augments allodynia in zoster via brain-derived neurotrophic factor.2010
Author(s)
Hama Y., Shiraki K., Yoshida Y., Maruyama A., Yasuda M., Tsuda M., Honda M., Takahashi M., Higuchi H., Takasaki I., Daikoku T., Tsumoto T.
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Journal Title
J.Virol. 84
Pages: 1616-1624
Related Report
Peer Reviewed
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[Journal Article] Antibody to varicella-zoster virus immediate-early protein 62 augments allodynia in zoster via brain-derived neurotrophic factor.2010
Author(s)
Hama Y., Shiraki K., Yoshida Y., Maruyama A., Yasuda M., Tsuda M., Honda M., Takahashi M., Higuchi H., Takasaki I., Daikoku T..Tsumoto T.
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Journal Title
J.Virol.84 : 1616-1624, 2010
Volume: 84
Pages: 1616-1624
Related Report
Peer Reviewed
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[Journal Article] Involvement of the serum response factor coactivator megakaryoblastic leukemia (MKL) in the activin-regulated dendritic complexity of rat cortical neurons.2010
Author(s)
Ishikawa, M., Nishijima, N., Shiota, J., Sakagami, H., Tsuchida, K., Mizukoshi, M., Fukuchi, M. Tsuda, M., Tabuchi, A.
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Journal Title
J.Biol.Chem.
Volume: 285
Pages: 32734-32743
Related Report
Peer Reviewed
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[Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) is an upstream regulator of prodynorphin mRNA expression in neurons.2010
Author(s)
Dong, Y.X., Fukuchi, M., Inoue, M., Takasaki, I., Tabuchi, A., Wu, C.F., Tsuda, M.
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Journal Title
Neurosci.Lett.
Volume: 484
Pages: 174-177
Related Report
Peer Reviewed
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[Journal Article] Activation of tyrosine hydroxylase (TH) gene transcription induced by brain-derived neurotrophic factor (BDNF) and its selective inhibition through Ca(2+) signals evoked via the N-methyl-D-aspartate (NMDA) receptor2010
Author(s)
Fukuchi, M., Fujii, H., Takachi, H., Ichinose, H., Kuwana, Y., Tabuchi, A., Tsuda, M.
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Journal Title
Brain Res.
Volume: 1366
Pages: 18-26
Related Report
Peer Reviewed
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[Presentation] G-protein-coupled receptor (GPCR) signaling induces activity-dependent gene expression through the modulation of N-methyl-D-aspartate receptor (NMDA-R) in neurons.2010
Author(s)
Tsuda, M., Fukuchi, M., Watanabe, S., Kuwana, Y., Takasaki, I., Tabuchi, A.
Organizer
The 40^<th> annual Meeting of the Society for Neuro science
Place of Presentation
San Diego, USA
Year and Date
2010-11-17
Related Report
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[Presentation] MKL, an actin-binding coactivator for SRF, is involved in TGF-beta family-induced alteration of dendritic morphology and transcriptional activity in rat cortical neurons.2010
Author(s)
Ishikawa, M., Nishijima, N., Shiota, J, Sakagami, H., Tsuchida, K., Tsuda, M., Tabuchi, A.
Organizer
The 40^<th> annual Meeting of the Society for Neuro science
Place of Presentation
San Diego, USA
Year and Date
2010-11-16
Related Report
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[Presentation] Isolation and characterization of rat SRF coactivator MKL1 splice variants differentially expressed in the developing brain.2010
Author(s)
Tabuchi, A., Hakamata, T., Ishikawa, M., Shiota, J., Shoji, S., Fukuchi, M., Tsuda, M.
Organizer
The 40^<th> annual Meeting of the Society for Neuro science
Place of Presentation
San Diego, USA
Year and Date
2010-11-16
Related Report
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