Regulation of Arc gene transcription by SRF cofactors: mechanism and application for drug design in ASD
| Project/Area Number |
26460064
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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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 |
TABUCHI Akiko 富山大学, 大学院医学薬学研究部(薬学), 准教授 (40303234)
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| Co-Investigator(Renkei-kenkyūsha) |
Mori Hisashi 富山大学, 大学院医学薬学研究部(医学), 教授 (00239617)
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| Research Collaborator |
FUKUCHI Mamoru 富山大学, 大学院医学薬学研究部(薬学), 助教
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 神経活動 / 血清応答因子(SRF) / MKL / Arc / 遺伝子発現 / 転写因子 / SRF / 脳由来神経栄養因子 / 血清応答因子 / 転写コファクター / 脳由来神経栄養因子(BDNF) |
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| Outline of Final Research Achievements |
Neuronal activity controls gene expression in neurons and regulates the amounts of molecules which are involved in brain function. Activity-regulated cytoskeleton-associated protein (Arc) functions at synapses. Thus, understanding the molecular mechanism of Arc gene expression contributes to the construction of drug design for neurological disorders. Transcription factors play a central role in gene expression. One of the representative transcription factor is serum response factor (SRF). We have focused on SRF-bound cofactor, megakaryoblastic leukemia (MKL). In this study, we found that MKL2 play an important role in activating Arc gene in neurons. In addition, SOLOIST, a novel MKL2 isoform, which we discovered activated several immediate early genes. We are now generating genetically modified mice to investigate the in vivo function of SOLOIST. Furthermore, we produced MKL1 and MKL2 antibodies.
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Report
(4 results)
Research Products
(38 results)
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[Journal Article] Neuromodulatory effect of Gαs- or Gαq-coupled GPCR on NMDAR selectively activates the NMDAR/Ca2+/calcineurin/CREB-regulated transcriptional coactivator 1 (CRTC1) pathway to effectively induce Bdnf expression in neurons.2015
Author(s)
Fukuchi M, Tabuchi A, Kuwana Y, Watanabe S, Inoue M, Takasaki I, Izumi H, Tanaka A, Inoue R, Mori H, Komatsu H, Takamori H, Okuno H, Bito H, Tsuda M.
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Journal Title
J Neurosci.
Volume: 35
Issue: 14
Pages: 5606-5624
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cellular localization and dendritic function of rat isoforms of the SRF coactivator MKL1 in cortical neurons.2014
Author(s)
Ishikawa M, Shiota J, Ishibashi Y, Hakamata T, Shoji S, Fukuchi M, Tsuda M, Shirao T, Sekino Y, Baraban JM, Tabuchi A.
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Journal Title
Neuroreport.
Volume: 25
Issue: 8
Pages: 585-92
DOI
Related Report
Peer Reviewed
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[Presentation] Identification and characterization of SOLOIST, a novel neuronal isoform of SRF coactivator MKL2: comparison to other MKL2 isoforms.2016
Author(s)
Tanaka T, Ishibashi Y, Shoji S, Kubo Y, Hakamata T, Sakagami H, Fukuchi M, Okuno H, Bito H, Tsuda M
Organizer
The First International Symposium on Toyama-Asia-Africa Pharmaceutical Network
Place of Presentation
Toyama
Year and Date
2016-09-12
Related Report
Int'l Joint Research
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