中枢シナプスの分子生物学

1994 Fiscal Year Annual Research Report

• Project/Area Number: 04267102
• Research Institution: The University of Tokyo
• Principal Investigator: 三品 昌美 東京大学, 医学部(医), 教授 (80144351)
• Co-Investigator(Kenkyū-buntansha): 伊藤 正男 理化学研究所, システム長 (90009887) ; 津本 忠治 大阪大学, 医学部, 教授 (50028619) ; 山本 長三郎 金沢大学, 医学部, 教授 (50008231) ; 吉岡 享 早稲田大学, 人間科学部, 教授 (70046027) ; 清水 孝雄 東京大学, 医学部(医), 教授 (80127092)
• Keywords: 中枢シナプス / 可塑性 / グルタミン酸受容体 / 逆行性伝達物質 / 神経伝達物質放出 / 長期増強 / 長期抑圧 / 総合的研究

Research Abstract

本重点領域研究は中枢シナプスにおける神経情報伝達素子の構造と機能を分子のレベルで明らかにすることを目的に、中枢における主要な興奮性神経伝達物質受容体であるグルタミン酸受容体の分子構造と生理機能、神経伝達物質放出の調節に関する機能分子およびシナプス後部から前部への逆行性情報伝達物質の探索の三点に的をしぼり研究を進めてきたが、中枢シナプス研究には総合的なアプローチが不可欠であり、本重点領域研究の総合的研究体制の促進および研究成果の評価と助言を行うために以下の会議等を開催した。
1.研究代表者および研究班長を中心にワーキンググループを作り、本重点領域研究の推進および共同研究の促進のための方策について検討した。
2.我が国の第一線の脳・神経研究者を含む総括班会議を開催し、本重点領域研究の推進と総合的研究への取り組みについて討議した。同時に、研究成果に対する評価と貴重な助言を頂いた。
3.班員全員が参加する班会議を開催し、計画班員と公募班員の全員が現在までの研究成果と今後の研究計画について発表し、すべての班員がこの発表を聞く機会を設けた。この班会議により班員すべてが互いによく知り合い、共同研究や研究協力を推進させることができた。
4.公開シンポジウムを開催するとともにニュースレターを発行することにより、本重点領域研究の目的、進展状況と成果、今後の中枢シナプス研究の展望ならびに中枢シナプス研究の重要性を広く知らせた。中枢シナプス機能分子の単離と測定法の開発が順調に進行しているのを受け、生理機能を分子レベルで理解することに重点を移し、研究費の重点的配分により、遺伝子ノックアウトマウスを用いた統合的中枢シナプス研究を推進した。

Research Products

• [Publications] Watanabe,M.: "Differential distributions of the NMDA receptor channel subunit mRNAs in the mouse retina." Brain Res.634. 328-332 (1994)
• [Publications] Watanabe,M.: "Distinct gene expression of the N-methyl-D-aspartate receptor channel subunit in peripheral neurons of the mouse sensory ganglia and adrenal gland." Neurosci. Lett.165. 183-186 (1994)
• [Publications] Ishida,N.: "Circadian expression of NMDA receptor mRNAs, ε3 and ζ1, in the suprachiasmatic nucleus of rat brain." Neurosci. Lett.166. 211-215 (1994)
• [Publications] Watanabe,M.: "Distinct spatio-temporal expressions of five NMDA receptor channel subunit mRNAs in the cerebellum." J. Comp. Neurol.343. 513-519 (1994)
• [Publications] Watanabe,M.: "Distinct distributions of five NMDA receptor channel subunit mRNAs in the brainstem." J. Comp. Neurol.343. 520-531 (1994)
• [Publications] Watanabe,M.: "Distinct spatio-temporal distributions of the NMDA receptor channel subunit mRNAs in the mouse cervical cord." J. Comp. Neurol.345. 314-320 (1994)
• [Publications] Nakano,R.: "A novel mutation in Cu/Zn superoxide dismutase gane in Japanese familial amyotrophic lateral sclerosis." Biochem. Biophys. Res. Commun.200. 695-703 (1994)
• [Publications] Kawamoto,S.: "Ligand binding properties and N-glycosylation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate(AMPA)-selective glutamate receptor channel expressed in a Baculovirus system." Eur. J. Biochem.223. 665-673 (1994)
• [Publications] Takahasi,H.: "Familial amyotrophic lateral sclerosis with a mutation in the Cu/Zn superoxide dismutase gene." Acta Neuropathol.88. 185-188 (1994)
• [Publications] Tsuzuki,K.: "Ion permeation properties of the cloned mouse ε2/ζ1 NMDA receptor channel." Mol. Brain Res.26. 37-46 (1994)
• [Publications] Hattori,S.: "Expression and characterization of the α2 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propinate(AMPA)-selective glutamate receptor channel in a Baculovirus system." Braih Res.666. 43-52 (1994)
• [Publications] Mori,H.: "Different spatio-temporal expressions of three otx homeoprotein transcripts during zebrafish embryogenesis." Mol. Brain Res.27. 221-231 (1994)
• [Publications] Hirano,T.: "Involvement of the glutamate receptor δ2 subunit in the long-term depression of glutamate responsiveness in cultured Purkinje cells." Neurosci. Lett.182. 172-176 (1994)
• [Publications] Sakimura. K.: "Reduced hippocampal LTP and spatial learning of mice lacking NMDA receptor ε1 subunit." Nature. 373. 151-155 (1995)
• [Publications] Hirano,T.: "Suppression of LTD in cultured Purkinje cells deficient of glutamate receptor δ2 subunit." Neuro Report. (印刷中). (1995)
• [Publications] Kawamoto,S.: "N-linked glycosylation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate(AMPA)-selectivc glutamate receptor channel α2 subunit is essential for the acquisition of ligand-binding activity." J.Neurochem.(印刷中). (1995)
• [Publications] Kawamoto,S.: "Expression and characterization of the ζ1 subunit of N-methyl-D-aspartate(NMDA) receptor channel in a Baculovirus system." Mol. Brain Res.(印刷中). (1995)
• [Publications] Yoshimura,Y.: "Dependance of LTP induction on postsynaptic depolarization: A proforated patch clamp study in visual cortical slices of young rats." J.Neurophysiol.71. 1638-1645 (1994)
• [Publications] Funauchi,M.: "Effects of an inhibitor for calcium/calmodulin-dependent protein phosphatase calcineurin, on induction of long-term potentiation in rat visual cortex." Neurosci. Res.19. 269-278 (1994)
• [Publications] Haruta,H.: "Induction of LTD but not LTP through metabotropic glutamate receptors in visual cortex." Neuro Report. 5. 1829-1832 (1994)
• [Publications] Harada,A.: "Altered microtubule organization in small-calibre axons of mice lacking tau protein." Nature. 36. 488-491 (1994)
• [Publications] Kondo,S.: "KIF3A is a new microtubules based fast anterograde motor in the nerve axons." J. Cell Biol.125. 1095-1107 (1994)
• [Publications] Nangaku,M.: "KIF1B;A new microtubule plus-end directed monomeric motor for mitochondria transport." Cell. 79. 1209-1220 (1994)
• [Publications] Suzuki,H.: "Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord." Br. J. Pharmacol.113. 310-316 (1994)
• [Publications] Hosoki,R.: "Effects of RP 67580,a tachykinin NK_1 receptor antagonist, on a primary afferent-evoked response of ventral roots in the neonatal rat spinal cord." Br. J. Pharmacol.113. 1141-1146 (1994)
• [Publications] Kawasaki,T.: "Regulation of calcium channel in sarcoplasmic reticulum by calsequestrin." Biochem. Biophys. Res. Commun.199. 1120-1127 (1994)
• [Publications] Kasai,M.: "Effects of KC1 concentrations on gating properties of calcium release channels in sarcoplasmic reticulum vesicls." J. Biochem.177(印刷中). (1995)
• [Publications] Hidari,K.: "A unique biosynthetic pathway for gangliosides exists in Xenopus leavis oocytes." FEBS Letters. 353. 25-28 (1994)
• [Publications] Nagai,Y.: "Significance of ganglioside-mediated glycosignal transduction in neuronal differentiation and development." “Biological Function of Gangliosides" (ed. Svennerholm, L. et al, Elsevier Sci., pp. 409,1994), Progress in Brain Reseach.101. 119-126 (1994)
• [Publications] Nara,K.: "Expression cloning of a CMP-NeuAc: NeuAcα2-3Galβ1-4GlcBl1'Cerα2, 8-sialyltransferase(GD3 Synthase) from human melanoma cells." Proc. Natl. Acad. Sci. USA. 91. 7952-7956 (1994)
• [Publications] Mochida,S.: "Impairment of syntaxin by botulinum neurotoxin Cl or antibodies inhibits acetylcholine release but not Ca^<2+> channel activity." Neurosci.65. (1995)
• [Publications] Nakade,S.: "Cyclic AMP-dependent phosphlylation of an immunoaffinity purified type I homoterameric inositol 1,4,5-trisphosphate receptor increases Ca^<2+> flux in reconstituted lipid vesicles." J. Biol. Chem.269. 6735-6742 (1994)
• [Publications] Michikawa,T.: "Transmembrane topology and site of N-Glycosylation of inositol 1,4,5-trisphosphate receptor" J. Biol. Cham.269. 9184-9189 (1994)
• [Publications] Fukuda,M.: "Inostiol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II." J. Biol. Chem.269. 29206-29211 (1994)
• [Publications] Arakane,F.: "Glycolipids isolated from Aplysia kurodai can activate cyclic adenosine 3',5'-monophosphosphate-dependent protein kinase from rat brain." J.Neurochem.62. 86-93 (1994)
• [Publications] Yamada,S.: "Structural analysis of a novel triphosphonoglycosphingolipid from the egg of the sea hare, Aplysia kurodai." J. Biochem.117(印刷中). (1995)
• [Publications] Ito,M.: "Is LTD associated with learning in the cerebellum?" Cellular and Molecular Mechanisms underlying Higher Neural Function. (eds. A. I. Selveston & P.Ascher, John Wiley & Sons). 15-40 (1994)
• [Publications] Karachot,L.: "Stimulus parameters for induction of long-term depression in in vitro slices of rat cerebellum." Neurosci. Res.21. 161-168 (1994)
• [Publications] Ajima,A.: "A unique role of protein phosphatase in induction of cerebellar long-term depression." Neuro Report. (印刷中). (1995)
• [Publications] Oyamada,H.: "Primary structure and distribution of ryanodine-binding protein isoforms of the bullfrog skeletal muscle." J. Biol. Chem.269. 17206-17214 (1994)
• [Publications] Tsukioka,M.: "pH dependence of inositol 1,4,5-trisphosphate-induced Ca^<2+> release in permeabilized smooth muscle cells of the guinea-pig." J. Physiol.475,3. 369-375 (1994)
• [Publications] Kasai,Y.: "Effects of cyclopiazonic acid on rhythmic contractions in uterine smooth muscle bundles of the rqt." Br. J. Pharmacol.112. 1132-1136 (1994)
• [Publications] Yamamoto,C.: "Suppression of hippocampal synaptic transmission by the spider toxin ω-agatoxin-IV-A." Brain Res.634. 349-352 (1994)
• [Publications] Ohno-Shousaku,T.: "A comparison between potencies of external calcium, strontium and barium to support GABAergic synaptic transmission in rat cultured hippocampal neurons." Neurosci. Res.20. 223-229 (1994)
• [Publications] Ohno-Shousaku,T.: "Contributions of multiple calcium channel types to GABAergic transmission in rat cultured hippocampal neurons." Neurosci. Lett.181. 145-148 (1994)
• [Publications] Nelson,T.J.: "Characterization of a GTP-binding protien implicated in both memory storage and interorganelle vesicle transport." Proc. Natl. Acad. Sci. USA. 91. 9287-9291 (1994)
• [Publications] Yamashima,T.: "Temperature-dependent Ca^<2+> mobilization induced by hypoxia-hypoglycemia in the monkey hippocampal slices." Biochem. Biophys. Res. Commun.205. 1843-1849 (1994)
• [Publications] Fikes,J.D.: "Distribution of gentamicin to the cochlea of the chicken embryo." Toxicol. Pathol.22. 15-22 (1994)
• [Publications] Honda,Z.: "Transfected platelet-activating factor receptor activates mitogen-activated protein(MAP) kinase and MAP kinase kinase in Chinese hamster ovary cells." J. Biol. Chem.269. 2307-2315 (1994)
• [Publications] Bito, H.: "Functional coupling of a rat hippocampal somatostain receptor to inhibition of adenylate cyclase, activation of arachidonate release and mitogen-activated(MAP) kinase." J. Biol. Chem.269. 12727-12730 (1994)
• [Publications] Takano, T.: "Role of cytoplasmic-tail phosphorylation sites of platelet-activating factor receptor in agonist-induced desensitization." J. Biol. Chem.269. 22453-22458 (1994)
• [Publications] Ferby,I.: "Wortmannin inhibits mitogen-activated protein kinase induced by platelet-activating factor in guinea-pig neutrophils." J. Biol. Chem.269. 30485-30488 (1994)
• [Publications] Nomura,A.: "Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells." Cell. 77. 361-369 (1994)
• [Publications] Nakanishi,S.: "Metabotropic glutamate receptors: synaptic transmission, modulation, and plasticity." Neuron. 13. 1031-1037 (1994)
• [Publications] Kaba,H.: "Induction of an olfactory memory by the activation of a metabotropic glutamate receptor." Science. 265. 262-264 (1994)
• [Publications] Ostuka,M.: "The Tachykinin Receptors, “Pharmacological characterization of receptors in the spinal cord of the newborn rat."" Ed.: S. H. Buck, Humana press, 15 (1994)
• [Publications] 葛西 道生: "膜学実験シリーズ 1「光散乱法」" 共立出版, 63 (1994)