| Project/Area Number |
23249013
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TEZUKA Tohru 東京大学, 医科学研究所, 助教 (50312319)
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| Co-Investigator(Renkei-kenkyūsha) |
NUREKI Osamu 東京大学, 理学系研究科, 教授 (10272460)
NATSUME Tohru 産業技術総合研究所, 創薬分子プロファイリング研究センター, センター長 (00357683)
TAKEDA Shin'ICHI 国立精神, 神経医療研究センター・神経研究所, 部長 (90171644)
MOTOMURA Masakatsu 長崎総合科学大学, 工学部, 教授 (70244093)
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| Project Period (FY) |
2011-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥48,360,000 (Direct Cost: ¥37,200,000、Indirect Cost: ¥11,160,000)
Fiscal Year 2013: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2012: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2011: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
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| Keywords | 細胞内シグナル伝達 / 神経筋シナプス / シグナル伝達 / 神経科学 |
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| Outline of Final Research Achievements |
We previously revealed that the cytoplasmic adaptor-like protein Dok-7 activates muscle-specific receptor tyrosine kinase MuSK, which is required for neuromuscular synaptogenesis and maintenance. To understand molecular signaling involved in neuromuscular synaptogenesis and myasthenia, we not only studied Dok-7 and MuSK-mediated signaling but also other signaling pathways in skeletal muscle. Our findings revealed that the chaperon protein Mesdc2 plays an important role in cell-surface expression of MuSK’s co-receptor Lrp4, which is essential for NMJ formation and maintenance. Also, we found that the MuSK activator agrin has a separate role in postnatal maintenance of NMJ. Furthermore, we developed an adeno-associated viral vector (AAV-D7), which expresses Dok-7, and showed that AAV-D7 treatment enlarged NMJs and restored motor activities of DOK7 myasthenia model mice, resulting in enhancement of their survival.
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