Elucidation of molecules and signaling pathways regulating neuromuscular junction formation

• Project/Area Number: 18K06127
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Ueta Ryo 東京大学, 医科学研究所, 助教 (10445025)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 神経生物学 / 神経筋シナプス / シグナル伝達

Outline of Final Research Achievements

Neuromuscular junction (NMJ) is an essential synapse between motor neuron and skeletal muscle.　The NMJ formation requires muscle specific receptor kinase MuSK and "NMJ formation signal"　that is driven by MuSK activation. To elucidate the mechanisms underlying NMJ formation, we have constructed the high-throughput screening system and identified candidate molecules that regulate NMJ formation. Moreover, we successfully enhanced the motor function and muscle strength of aged mice by modulating NMJ formation signal.

Academic Significance and Societal Importance of the Research Achievements

本研究は我々の運動機能制御に必須のNMJについて、その成り立ちの理解を深める点において学術的な意義を有する。加えて、本研究成果は、NMJ形成増強治療が加齢性の運動機能・筋力低下に有効である可能性を提示するもので、高齢化社会における生活の質の向上に資する医療技術としての発展が期待される点において社会的意義を有する。

Research Products

• [Journal Article] DOK7 Gene Therapy Enhances Neuromuscular Junction Innervation and Motor Function in Aged Mice (2020)
  • Author(s): Ueta R, Sugita S, Minegishi Y, Shimotoyodome A, Ota N, Ogiso N, Eguchi T, Yamanashi Y
  • Journal Title: iScience Volume: 23 Issue: 8 Pages: 101385-101385
  • DOI: 10.1016/j.isci.2020.101385
  • Peer Reviewed / Open Access