Functional roles of IQ-ArfGEF at excitatory postsynaptic sites

• Project/Area Number: 23700416
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Kitasato University
• Principal Investigator: FUKAYA Masahiro 北里大学, 医学部, 講師 (10360900)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: IQ-ArfGEF / 精神遅滞 / ノックアウトマウス / シナプス / 遺伝子欠損マウス / 中枢神経 / 知的障害

Research Abstract

In this study, I focused on IQ-ArfGEF, one of the excitatory postsynaptic molecules, which causes nonsyndromic mental retardation. To reveal the functional mechanisms of IQ-ArfGEF at postsynaptic sites, IQ-ArfGEF knockout mice were generated. Using IQ-ArfGEF knockout mice, many neuronal and glial marker molecules were screened by immunoblot and immunohistochemical assays. Consequently, impairment of IQ-ArfGEF was accompanied by upregulation of some neural molecules in the brain.

Research Products

• [Journal Article] Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis (2013)
  • Author(s): Kang S, Li Y, Fukaya M, Lorenzini I, Cleveland DW, Ostrow LW, Rothenstein JD, Bergles DE
  • Journal Title: Nat Neurosci Volume: 16(5) Issue: 5 Pages: 571-579
  • DOI: 10.1038/nn.3357
  • Peer Reviewed
• [Journal Article] Distinct synaptic localization patterns of brefeldin A-resistant guanine nucleotide exchange factors BRAG2 and BRAG3 in the mouse retina (2013)
  • Author(s): Sakagami H, Katsumata O, Hara Y, Tamaki H, Watanabe M, Harvey RJ, Fukaya M
  • Journal Title: J. Comp. Neurol Volume: 521 Issue: 4 Pages: 860-876
  • DOI: 10.1002/cne.23206
  • Peer Reviewed
• [Journal Article] Accumulation of a-synuclein triggered by presynaptic dysfunction (2012)
  • Author(s): Nakata Y, Yasuda T, Fukaya M, Yamamori S, Itakura M, Nihira T, Hayakawa H, Kawanami A, Kataoka M, Nagai M, Sakagami H, Takahashi M, Mizuno Y, Mochizuki H
  • Journal Title: J. Neurosci Volume: 32 Issue: 48 Pages: 17186-17196
  • DOI: 10.1523/jneurosci.2220-12.2012
  • Peer Reviewed
• [Journal Article] Mitochondrial Division Ensures the Survival of Postmitotic Neurons by Suppressing Oxidative Damage (2012)
  • Author(s): Kageyama Y, Zhang Z, Roda R, Fukaya M, Wakabayashi J, Wakabayashi N, Kelsler TW, Reddy H, Iijima M, Sesaki H
  • Journal Title: J Cell Biol Volume: 197(4) Issue: 4 Pages: 535-551
  • DOI: 10.1083/jcb.201110034
  • Peer Reviewed
• [Journal Article] Pilt is a coiled-coil domain-containing protein that localizes at the trans-Golgi complex and regulates its structure (2012)
  • Author(s): Tamaki H, Sanda M, Katsumata O, Hara Y, Fukaya M, Sakagami H
  • Journal Title: FEBS Lett Volume: 586 Issue: 19 Pages: 3064-3070
  • DOI: 10.1016/j.febslet.2012.07.051
  • Peer Reviewed
• [Journal Article] SynArfGEF is a guanine nucleotide exchange factor for Arf6 and localies preferentially at post-synaptic specializations of inhibitory synapses (2011)
  • Author(s): Fukaya M, Kamata A, Hara Y, Tamaki H, Katsumata O, Ito N, Takeda S, Hata Y, Suzuki T, Watanabe M, Harvey RJ, Sakagami H
  • Journal Title: Journal of Neurochemistry Volume: 116 Pages: 1122-1137
  • Peer Reviewed
• [Presentation] Splice variant-dependent subcellular localization of the Arf6 activator BRAG2 in the adult mouse brain (2013)
  • Author(s): 深谷昌弘、阪上洋行
  • Organizer: Splice variant-dependent subcellular localization of the Arf6 activator BRAG2 in the adult mouse brain
  • Place of Presentation: 高松
• [Presentation] Splice variant-dependent subcellular localization of the Arf6 activator BRAG2 in the adult mouse brain (2013)
  • Author(s): 深谷昌弘
  • Organizer: 第１１８回 日本解剖学会全国学術集会
  • Place of Presentation: 高松
• [Presentation] 成体マウス脳におけるARF6活性化因子BRAG2/IQSEC1の細胞内局在解析 (2012)
  • Author(s): 深谷昌弘、原芳伸、阪上洋行
  • Organizer: 第１１７回 日本解剖学会全国学術集会
  • Place of Presentation: 甲府（山梨大学）
• [Presentation] Postsynaptic and endosomal localization of BRAG2/GEP100 in the adult mouse brain (2011)
  • Author(s): 深谷昌弘、原芳伸、阪上洋行
  • Organizer: 第３４回 日本神経科学大会
  • Place of Presentation: 横浜（パシフィコ横浜）