Role of local protein synthesis regulated by Fragile X Mental Retardation Protein during presynapse formation

• Project/Area Number: 25430068
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Yokohama City University
• Principal Investigator: SASAKI Yukio 横浜市立大学, 生命医科学研究科, 准教授 (10295511)
• Co-Investigator(Renkei-kenkyūsha): KAWAKAMI Takao 横浜市立大学, 生命医科学研究科, 客員准教授 (40366117)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 横浜市 / 神経生物学 / 脆弱X症候群 / シナプス / プロテオミクス

Outline of Final Research Achievements

To investigate to a role of local protein synthesis during presynapse differentiation in neurons, we identified proteins that accumulate in axons during presynapse differentiation. Most of the identified proteins are derived from the target mRNA for FMRP (Fragile X Mental Retardation Proteins), the RNA-binding protein. Among these proteins, we examined Munc-18 accumulation during the presynapse differentiation. The accumulation time-course of Munc-18 corresponded to that of Argonaute2 (Ago2), which interacts with FMRP. Thus, it is possible that FMRP-Ago2 complex regulate Munc-18 expression via local protein synthesis during presynapse differentiation.

Research Products

• [Journal Article] Identification of axon-enriched MicroRNAs localized to growth cones of cortical neurons. (2014)
  • Author(s): Sasaki Y, Gross C, Xing L, Goshima Y, Bassell GJ.
  • Journal Title: Dev Neurobiol Volume: 74 Issue: 3 Pages: 397-406
  • DOI: 10.1002/dneu.22113
  • Peer Reviewed
• [Journal Article] Plexin-A4-dependent retrograde semaphorin 3A signalling regulates the dendritic localization of GluA2-containing AMPA receptors. (2014)
  • Author(s): Yamashita N, Usui H, Nakamura F, Chen S, Sasaki Y, Hida T, Suto F, Taniguchi M, Takei K, Goshima Y.
  • Journal Title: Nat Commun Volume: 5 Pages: 3424-3424
  • Peer Reviewed
• [Presentation] シナプス前終末形成過程におけるマイクロRNA結合タンパク質Argonaute2の局在変化 (2015)
  • Author(s): 高橋 徹、杉浦 侑、佐々木 幸生
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートピアアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-03
• [Presentation] セマフォリン3Aは脆弱X精神遅滞タンパク質のユビキチン化を誘導する (2014)
  • Author(s): 高畠 将、五嶋 良郎、佐々木 幸生
  • Organizer: 第130回日本薬理学会関東部会
  • Place of Presentation: 星薬科大学(東京都品川区）
  • Year and Date: 2014-07-05
• [Presentation] 脆弱X精神遅滞タンパク質の軸索・成長円錐における局在はセマフォリン3Aにより制御される (2013)
  • Author(s): 佐々木 幸生、髙畠 将、花岡 和則、五嶋 良郎
  • Organizer: 第36回日本神経科学大会、第56回日本神経化学会大会、第23回日本神経回路学会大会合同大会（Neuro2013）
  • Place of Presentation: 京都
• [Presentation] 新規培養法「ニューロンボール法」を用いたシナプス前終末形成のプロテオーム解析 (2013)
  • Author(s): 佐々木 幸生
  • Organizer: 第35回神経組織培養研究会
  • Place of Presentation: 吹田
• [Presentation] セマフォリン 3Aによる脆弱X精神遅滞タンパク質の局在制御 (2013)
  • Author(s): 高畠 将、五嶋 良郎、佐々木 幸生
  • Organizer: 第15回RNA学会年会
  • Place of Presentation: 松山
• [Presentation] Proteomics of axons during presynapse formation using the novel culture method "neuron ball culture" (2013)
  • Author(s): Sasaki Y, Ishikawa A, Kawakami T, Hirano H, Goshima Y.
  • Organizer: 12th HUPO
  • Place of Presentation: 横浜
• [Presentation] 高畠 将、五嶋 良郎、佐々木 幸生 (2013)
  • Author(s): セマフォリン3Aによる脆弱X精神遅滞タンパク質のユビキチン化
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸