Molecular mechanisms of the formation and maintenance of NMJs

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460357
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: TEZUKA Tohru 東京大学, 医科学研究所, 助教 (50312319)
• Co-Investigator(Renkei-kenkyūsha): Yamanashi Yuji 東京大学, 医科学研究所, 教授 (40202387)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 神経科学 / 神経筋接合部

Outline of Final Research Achievements

The formation and maintenance of neuromuscular junctions (NMJs), a synapse essential for motoneural control of skeletal muscle contraction, is governed by the muscle-specific receptor-tyrosine kinase MuSK. Activation of MuSK involves Agrin, Lrp4, and Dok-7. Dok-7 is an essential muscle-intrinsic activator of MuSK. On the other hand, motor neuron-derived MuSK activator Agrin binds to MuSK’s co-receptor Lrp4 and indirectly activates MuSK. In the current study, by analysis of muscle-specific Dok-7 transgenic mice lacking Lrp4, we demonstrated that Lrp4 is required for efficient activation of MuSK by Dok-7 in vivo. In addition, using recombinant adeno-associated virus vectors carrying short hairpin RNAs targeting the mouse dok-7 gene, we showed that the correct, physiological level of dok-7 gene expression is critical for the postnatal maintenance of NMJs.

Free Research Field

分子生物学