Roles of Dok-7 and MuSK in neuromuscular synaptogenesis

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790266
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: TEZUKA Tohru The University of Tokyo, 医科学研究所, 助教 (50312319)
• Project Period (FY): 2009 – 2010
• Keywords: 神経筋接合部 / シグナル伝達 / チロシンリン酸化

Research Abstract

The neuromuscular junction (NMJ) is a synapse between a motor neuron and skeletal muscle. Defects in the formation and function of the NMJ are associated with neuromuscular disorders such as congenital myasthenic syndromes and myasthenia gravis. The muscle-specific receptor tyrosine kinase MuSK and its cytoplasmic activator Dok-7 are essential for the formation of the NMJ. To understand the molecular mechanism underlying Dok-7-mediated activation of MuSK and intracellular signaling evoked by activation of MuSK, we carried out proteomic studies. We identified proteins that bound to MuSK and Dok-7, and those that were phosphorylated upon activation of MuSK in cultured myotubes. Roles of these proteins in the formation and function of the NMJ are under investigation.

Research Products

• [Journal Article] NMDAR2B tyrosine phosphorylation regulates anxiety-like behavior and CRF expression in the amygdala. (2010)
  • Author(s): Delawary M, Tezuka T, Kiyama Y, Yokoyama K, Inoue T, Hattori S, Hashimoto R, Umemori H, Manabe T, Yamamoto T, Nakazawa T.
  • Journal Title: Mol Brain. 3 Pages: 37
  • Peer Reviewed
• [Journal Article] Involvement of NMDAR2A tyrosine phosphorylation in depression-related behaviour. (2009)
  • Author(s): Taniguchi S, Nakazawa T, Tanimura A, Kiyama Y, Tezuka T, Watabe AM, Katayama N, Yokoyama K, Inoue T, Izumi-Nakaseko H, Kakuta S, Sudo K, Iwakura Y, Umemori H, Inoue T, Murphy NP, Hashimoto K, Kano M, Manabe T, Yamamoto T.
  • Journal Title: EMBO J. 28(23) Pages: 3717-3729
  • Peer Reviewed
• [Journal Article] The roles of Dok family adapters in immunoreceptor signaling. (2009)
  • Author(s): Mashima R, Hishida Y, Tezuka T, Yamanashi Y.
  • Journal Title: Immunol Rev. 232(1) Pages: 273-285
  • Peer Reviewed
• [Presentation] Involvement of NMDAR2A tyrosine phosphorylation in depression-related behavior. (2009)
  • Author(s): 中澤敬信、谷口幸子、谷村あさみ、城山優治、手塚徹、狩野方伸、真鍋俊也、山本雅
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] The Novel NYAP phosphoprotein family couples activation of phosphoinositide 3-kinase (PI3K) p85 with the cytoskeletal WAVE signaling pathway in the brain. (2009)
  • Author(s): 横山一剛、手塚徹、小谷政晴、中澤敬信、星名直祐、井上毅、霜田靖、角田茂、須藤カツ子、渡邉和忠、岩倉洋一郎、山本雅
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Book] 生体の科学(先天性筋無力症の分子基盤、Vol.62 No.2) (2011)
  • Author(s): 手塚徹、山梨裕司
  • Total Pages: 106-111
  • Publisher: 医学書院
• [Remarks] ホームページ等
• [Remarks] 研究代表者が所属する研究室のホームページ
  • URL: http://www.ims.u-tokyo.ac.jp/genetics/html/home.html