Signaling from synapses to the nucleus by transcription factor MKL, which is a risk candidate for psychiatric and neurodevelopmental disorders
| Project/Area Number |
18K06625
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
|
|---|
| Research Institution | University of Toyama |
|---|
Principal Investigator |
TABUCHI Akiko 富山大学, 学術研究部薬学・和漢系, 准教授 (40303234)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 血清応答因子(SRF) / 神経活動 / MKL / 遺伝子発現 / 転写因子 / MRTF / SRF / シナプス / 神経細胞 / 神経疾患 |
|---|
| Outline of Final Research Achievements |
The SNPs or mutations of SRF transcriptional cofactor MKL1 (MRTFA) or MKL2 (MRTFB) gene is a possible risk factor for neurological disorders. Thus, understanding for molecular mechanisms underlying MKL-mediated gene expression contributes to elucidation of the etiology of neurological disorders. Here we have demonstrated that MKL2 mediates activation of the Arc enhancer, synaptic activity-responsive element of activity-regulated cytoskeleton-associated protein (Arc) gene induced by BDNF. In addition, neuronal activity-dependent nuclear translocation of MKL2 from synapses is mediated by an NMDA receptor and an L-type voltage-dependent calcium channel, and followed by phosphatase calcineurin. On the other hand, neuronal activity induces Rho GTPase-dependent F-actin polymerization, which is required for nuclear translocation of MKL2.
|
| Academic Significance and Societal Importance of the Research Achievements |
神経機能遺伝子の発現を合理的かつ効率的に活性化する仕組みを解明でき、シナプスの安定化や維持、記憶学習の本質を明らかにできる。また、本研究に用いた研究材料や技術を国内外の研究者らに提供することにより、神経科学分野のみならず、MKLの関わりが指摘されるがん転移分野などの生命科学分野の発展に貢献する。
MKLをターゲットとして精神疾患・発達障害の治療や予防に役立てることができる。MKLの核移行促進やMKL活性化を引き起こす低分子化合物、将来的には食品成分を同定することで、メンタルヘルス（精神衛生）の向上につながり、患者や家族のQOLの改善、脳の活性化を基軸とした健康寿命の延伸に役立つ。
|
Report
(4 results)
Research Products
(18 results)
-
[Journal Article] Involvement of SRF coactivator MKL2 in BDNF-mediated activation of the synaptic activity-responsive element in the Arc gene.2019
Author(s)
Kikuchi K, Ihara D, Fukuchi M, Tanabe H, Ishibashi Y, Tsujii J, Tsuda M, Kaneda M, Sakagami H, Okuno H, Bito H, Yamazaki Y, Ishikawa M, Tabuchi A.
-
Journal Title
Journal of Neurochemistry
Volume: 148
Issue: 2
Pages: 204-218
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
[Presentation] Synaptic localization of SRF coactivators MKL1 (MRTF-A) and MKL2 (MRTF-B) and their function in dendritic morphology were elucidated by generation and evaluation of new antibodies against MKL1 and MKL2。2018
Author(s)
Kaneda M, Sakagami H, Hida Y, Ohtsuka T, Satou N, Ishibashi Y, Fukuchi M, Krysiak A, Ishikawa M, Ihara D, Kalita K, Tabuchi A
Organizer
International MADS Box Conference 2018
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
