競合的シナプス回路成熟の構造基盤と分子基盤

2006 Fiscal Year Annual Research Report

• Project/Area Number: 17023001
• Research Institution: Hokkaido University
• Principal Investigator: 渡辺 雅彦 北海道大学, 大学院医学研究科, 教授 (70210945)
• Keywords: 小脳 / シナプス / グルタミン酸 / 発達 / 遺伝子改変動物

Research Abstract

本研究では、活動依存的な競合を基盤とするシナプス回路の強化と除去を決定する分子機構を解明することを目的とする。これにより、異種入力間(小脳)と同種入力間(大脳)の競合によるシナプス回路発達の共通原理の解明を目指す。
平成18年度において、シナプス活動依存的な基盤となる情報伝達分子であるホスフォリパーゼCβ(PLCβ)、AMPA型グルタミン酸受容体の調節分子であるTARP-g8、小脳シナプス形成制御分子であるCbln1を含む分子ファミリーなどの遺伝子発現と分子局在等を明らかにした。その結果、PLCβ3はPLCβ4の発現が弱い小脳後葉のプルキンエ細胞に選択的に発現し、樹状突起や棘突起に加え軸索にも発現分布していた。この事実は、この2つのPLCサブタイプが小脳情報伝達に関与する効果器酵素であることを示した。TARP-g8は大脳皮質や海馬などの終脳に強く発現し、シナプス膜および非シナプス膜の両方に発現していることを明らかにした。さらに、その遺伝子欠損により海馬のAMPA受容体の発現とシナプス応答が著明に減少した。したがって、この分子が海馬の興奮性シナプス伝達を担う制御分子であることが明らかになった。Cbln1と3は小脳に豊富であるが、Cbln1,2,4は小脳以外にも発現しそれぞれ異なる脳内発現をしていることが明らかとなった。従って、小脳以外のシナプス形成にもCblnファミリーが関与している可能性が示唆された。

Research Products

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  • Peer Reviewed
• [Journal Article] Characterization of a novel low-molecular-mass dual specificity phosphatase-4 (LDP-4) expressed in brain. (2007)
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  • Journal Title: Mol. Cell. Biochem. 296 Pages: 177-184
• [Journal Article] Number and density of AMPA receptors in individual synapses in the cerebellum as revealed by SDS-digested freeze-fracture replica labeling. (2007)
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  • Journal Title: Eur. J. Neurosci. 25 Pages: 659-672
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• [Journal Article] Characterization of a transneuronal cytokine family Cbln. regulation of secretion by heteromeric assembly. (2007)
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• [Journal Article] Segmental and complementary expression of L-serine biosynthetic enzyme 3-phosphoglycerate dehydrogenase and neutral amino acid transporter ASCT1 in the mouse kidney. (2007)
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  • Journal Title: Biomed Res (in press)
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  • Peer Reviewed
• [Journal Article] NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity. (2006)
  • Author(s): Nakazawa T, Komai S, Watabe AM, 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
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  • Peer Reviewed
• [Journal Article] Impaired cerebellar functions in mutant mice lacking DNER. (2006)
  • Author(s): Tohgo A, Eiraku M, Miyazaki T, Miura E, Ono K, Kawaguchi S, Nishi M, Watanabe M, Hirano T, Kengaku M, Takeshima H
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  • Peer Reviewed
• [Journal Article] Complementary stripes of phospholipase Cβ3 and Cβ4 expression by Purkinje cell subsets in the mouse cerebellum. (2006)
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• [Journal Article] Improved methods for ultracryotomy of CNS tissue for ultrastructural and immunogold analyses. (2006)
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• [Journal Article] The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic site in the hippocampus and cerebellum. (2006)
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• [Journal Article] Expression and distribution of JNK/SAPK-associated scaffold protein JSAP1 in developing and adult mouse brain. (2006)
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• [Journal Article] Diacylglycerol kinase ζ is involved in the process of cerebral infarction. (2006)
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• [Journal Article] Localization of diacylglycerol lipase-α around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. (2006)
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• [Journal Article] Phenotyping of sensory and sympathetic ganglion neurons of a galanin-overexpressing mouse-Possible implications for pain processing. (2006)
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• [Journal Article] Effects of RNA interference of Atg4B on the limited proteolysis of LC3 in PC12 cells an expression of Atg4B in various rat tissues. (2006)
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  • Journal Title: Autophagy 2 Pages: 200-208
• [Journal Article] Gene expression and localization of diacylglycerol kinase isozymes in the rat spinal cord and dorsal root ganglia. (2006)
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• [Journal Article] Distinct expression of Cbln family mRNAs in developing and adult mouse brains. (2006)
  • Author(s): Miura E, Iijima T, Yuzaki M, Watanabe M(Corresponding author)
  • Journal Title: Eur. J. Neurosci. 24 Pages: 750-760
• [Journal Article] Functional uncoupling between Ca^<2+> release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins. (2006)
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• [Journal Article] Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family. (2006)
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  • Journal Title: FEBS Lett. 580 Pages: 4057-4064
• [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(Corresponding author)
  • Journal Title: Eur. J. Neurosci. 24 Pages: 2177-2190
• [Journal Article] Depolarization-induced suppression of inhibition mediated by endocannabinoid at synapses from fast-spiking interneurons to medium spiny neurons in the striatum. (2006)
  • Author(s): Narushima M, Uchigashima M, Hashimoto K, Watanabe M, Kano M
  • Journal Title: Eur. J. Neurosci. 24 Pages: 2246-2252
• [Journal Article] ATP-binding cassette transporter G2 mediates the efflux of phototoxins on the luminal membrane of retinal capillary endothelial cells. (2006)
  • Author(s): Asashima T, Hori S, Ohtsuki S, Tachikawa M, Watanabe M, Mukai C, Kitagaki S, Miyakoshi N, Terasaki T
  • Journal Title: Pharmacol. Res. 23 Pages: 1235-1242