バーグマングリアに発現するグルタミン酸受容体結合分子の機能的役割

• Project/Area Number: 18053001
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Hokkaido University
• Principal Investigator: 深谷 昌弘 Hokkaido University, 大学院・医学研究科, 助教 (10360900)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥6,100,000 (Direct Cost: ¥6,100,000); Fiscal Year 2007: ¥3,100,000 (Direct Cost: ¥3,100,000); Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
• Keywords: AMPA受容体 / バーグマングリア / stargazinファミリー / TARPs / ノックアウトマウス / 小脳 / 神経科学 / グルタミン酸受容体

Research Abstract

本研究では小脳バーグマングリアに発現するAMPA型グルタミン酸受容体およびその結合分子であるStargazinファミリー(TARPs)の詳細な細胞内局在解析を行い、バーグマングリアに発現するStargazinファミリーであるγ5サブユニットのノックアウトマウスを用いて、バーグマングリアでのAMPA型グルタミン酸受容体の発現調節機構を分子解剖学的に明らかにすることを目的として研究を行った。その結果、バーグマングリアに発現するAMPA型グルタミン酸受容体とγ5は共に平行線維および登上線維が形成する興奮性シナプスのシナプス間隙に面するバーグマングリアの突起の細胞膜に局在していた。また、バーグマングリアの細胞体内部のゴルジ装置に囲まれた小胞にも局在し、これらの分子が貯留していることが認められた。さらに、γ5サブユニットノックアウトマウスでは、このAMPA受容体のバーグマングリア細胞体内での貯留が消失し、グリア突起による不完全なシナプス被覆が認められた。以上の結果からバーグマングリアにおけるAMPA受容体は放出されたグルタミン酸を効率よく受容できる部位に局在するように制御を受けており、γ5はAMPA受容体の細胞体から突起への輸送を調節していることが示唆された。ニューロンではこのようなAMPA型グルタミン酸受容体の細胞体での貯留等は認められないことから、バーグマングリアではニューロンとは異なった受容体の局在調節機構が存在する可能性が示唆された。

Research Products

• [Journal Article] Axonal motility and its modulation by activity are branch-type specific in the intact adult cerebellum (2007)
  • Author(s): Nishiyama H, Fukaya M, Watanabe M, Linden D
  • Journal Title: Neuron 56 Pages: 472-487
  • Peer Reviewed
• [Journal Article] Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and non-motoneuronal phenotypes (2007)
  • Author(s): Niemann S, Kanki H, Fukui Y, Takao K, Fukaya M, Hynynen MN, Churchill MJ, Shefner JM, Bronson RT, Watanabe M, Brown RHJr, Miyakawa T, Itohara S, Hayashi Y
  • Journal Title: European Journal of Neuroscience 26 Pages: 1407-1420
  • Peer Reviewed
• [Journal Article] Evidence against GABA release from glutamatergic mossy fiber terminals in the developing hippocampus (2007)
  • Author(s): Uchigashima M, Fukaya M, Watanabe M, Kamiya H
  • Journal Title: The Journal of Neuroscience 27 Pages: 8088-8100
  • Peer Reviewed
• [Journal Article] Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum (2007)
  • Author(s): Uchigashima M, Narushima M, Fukaya M, Katona I, Kano M, Watanabe M
  • Journal Title: The Journal of Neuroscience 27 Pages: 3663-3676
  • NAID: 120005183167
  • Peer Reviewed
• [Journal Article] Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity (2007)
  • Author(s): Kakizawa S, Kishimoto Y, Hashimoto K, Miyazaki T, Furutanil K, Shimizu H, Fukaya M, Nishi M, Sakagami H, Ikeda A, Kondo H, Kano M, Watanabe M, Iino M, Takeshima H
  • Journal Title: EMBO Journal 26 Pages: 1924-1933
  • Peer Reviewed
• [Journal Article] Vesicular release of glutamate from unmyelinated axons in white matter (2007)
  • Author(s): Ziskin J L, Nishiyama A, Rubio M, Fukaya M, Bergles DE
  • Journal Title: Nature Neuroscience 10 Pages: 321-330
  • Peer Reviewed
• [Journal Article] Phospholipase Cb3 is distributed in both somatodendriteic and axonal compartments and localized around perisynapse and smooth endoplasmic reticulum in mouse Purkinje cell subsets (2007)
  • Author(s): Nomura S, Fukaya M, Tsujioka T, Wu D, Watanabe M
  • Journal Title: European Journal of Neuroscience 25 Pages: 659-672
  • Peer Reviewed
• [Journal Article] Tonic enhancement of endocannabinoid-mediated retrograde suppression of inhibition by cholinergic interneuron activity in the striatum (2007)
  • Author(s): Narushima M, Uchigashima M, Fukaya M, Matsui M, Manabe T, Hashimoto K, Watanabe M, Kano M
  • Journal Title: The Journal of Neuroscience 27 Pages: 496-506
  • Peer Reviewed
• [Journal Article] Phospholipase Cβ3 is distributed in both somatodendriteic and axonal compartments and localized around perisynapse and smooth endoplasmic reticulum in mouse Purkinje cell subsets (2007)
  • Author(s): Nomura S, Fukaya M, Tsujioka T, Wu D, Watanabe M
  • Journal Title: European Journal of Neuroscience (in press)
• [Journal Article] Vesicular release of glutamate from unmyelinated axons in white matter (2007)
  • Author(s): Ziskin J L, Nishiyama A, Rubio M, Fukaya M, Bergles D E
  • Journal Title: Nature Neuroscience (in press)
• [Journal Article] Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity (2007)
  • Author(s): Kakizawa S, Kishimoto Y, Hashimoto K, Miyazaki T, Furutanil K, Shimizu H, Fukaya M, Nishi M, Sakagami H, Ikeda A, Kondo H, Kano M, Watanabe M, Iino M, Takeshima H
  • Journal Title: The EMBO Journal (in press)
• [Journal Article] Abundant distribution of TARP γ-8 in synaptic and extrasynaptic surface of hippocampal neurons and its major role in AMPA receptor expression on spines and dendrites (2006)
  • Author(s): Fukaya M, Tsujita M, Yamazaki M, Kushiya E, Abe M, Akashi K, Natsume R, Kano M, Kamiya H, Watanabe M, Sakimura K
  • Journal Title: European Journal of Neuroscience 24 Pages: 2177-2190
  • NAID: 120000955769
• [Journal Article] Effects of RNA interference of Atg4B on the limited proteolysis of LC3 in PC12 cells and expression of Atg4B in various tissues (2006)
  • Author(s): Yoshimura K, Shibata M, Gotoh K, Fukaya M, Watanabe M, Uchiyama Y
  • Journal Title: Autophagy 2・3 Pages: 200-208
• [Journal Article] NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity (2006)
  • Author(s): Nakazawa T, Komai S, Watabe MA, Kiyama Y, Fukaya M, Arima-Yoshida F, Horai R, Sudo K, Ebine K, Delawary M, Goto J, Umemori H, Tezuka T, Iwakura Y, Watanabe M, Yamamoto T, Manabe T
  • Journal Title: The EMBO Journal 25 Pages: 2867-2877
• [Journal Article] Localization of diacylglycerol lipase-a around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor (2006)
  • Author(s): Yoshida T, Fukaya M, Uchigashima M, Miura E, Kamiya H, Kano M, Watanabe M
  • Journal Title: The Journal of Neuroscience 26・18 Pages: 4740-4751
• [Journal Article] The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum (2006)
  • Author(s): Kawamura Y, Fukaya M, Maejima T, Yoshida T, Miura E, Watanabe M, Ohno-Shosaku T, Kano M
  • Journal Title: The Journal of Neuroscience 26・18 Pages: 2991-3001
  • NAID: 120007186992
• [Journal Article] Expression and distribution of JNK/SAPK-associated scaffold protein JSAP1 in developing and adult mouse brain (2006)
  • Author(s): Miura E, Fukaya M, Sato T, Sugihara K, Asano M, Yoshioka K, Watanabe M
  • Journal Title: Journal of Neurochemistry 97 Pages: 1431-1446
• [Presentation] Selective localization of NR3A subunit at climbing fiber-interneuron synapses in the cerebellum (2007)
  • Author(s): Masahiro Fukaya and Masahiko Watanabe
  • Organizer: Society for Neuroscience 37th Annual Meeting
  • Place of Presentation: サンディエゴコンベンションセンター・San Diego, USA
• [Presentation] The mode of AMPA-type glutamate receptor trafficking in Bergmannglia (2007)
  • Author(s): 深谷昌弘、渡辺雅彦
  • Organizer: 第30回 日本神経科学大会
  • Place of Presentation: 横浜・パシフィコ横浜
• [Presentation] 小脳における登上線維-介在ニューロン間シナプス選択的に発現するNMDA受容体NR3Aサブユニットの分子解剖学的解析 (2007)
  • Author(s): 深谷昌弘、渡辺雅彦
  • Organizer: 日本解剖学会第53回東北・北海道連合支部学術集会
  • Place of Presentation: 札幌・北海道医療大学