| Project/Area Number |
21590274
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | University of Fukui |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MURAMATSU Ikunobu 福井大学, 医学部, 教授 (10111965)
SUZUKI Fumiko 福井大学, 医学部, 助教 (80291376)
ROMISHIMA Shigeru 福井大学, 医学部, 准教授 (50290911)
UWADA Junsuke 福井大学, 医学部, 助教 (70580314)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 中枢 / 末梢神経 / SUMO化 / シナプス伝達 / 翻訳後修飾 / 神経伝達物質受容体 / 細胞内トラフィキング |
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| Research Abstract |
We found that pre-synaptic regulatory function of protein SUMOylation. Introduction of the recombinantly expressed and purified SUMO1 protein into the presynaptic terminal significantly inhibited depolarization-evoked glutamate release from the synaptosomes. On the other hand, introduction of the catalytic domain of the de-SUMOylation enzyme SENP1 enhanced the glutamate release. These results strongly suggested that glutamate release from the synaptic terminal is negatively regulated via protein SUMOylation. In addition, we identified novel SUMOylation substrates at synapses such as mGluR7 or GISP(GPCRs-interacting scaffolding protein). In the all cases thus far examined, synaptic protein SUMOylation is depending upon neuronal activities to some extent. Finally, we developed the SUMOylation substrates trapping constract by fusing active SUMO1/2 with tandem affinity purification tag. Our preliminary application of this construct to the primary cortical neurons validated the concept.
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