グリシン作動性興奮性受容体は対称性と非対称性のどちらのシナプスに発現するか?

• Project/Area Number: 17650087
• Research Category: Grant-in-Aid for Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Neuroscience in general
• 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)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: グルタミン / グリシン / NMDA / シナプス / 興奮性 / 抑制性 / グルタミン酸受容体 / NMDA受容体 / NR3 / 免疫電顕

Research Abstract

グルタミン酸は脳における主要な興奮性神経伝達物質で、シナプスにおけるグルタミン酸受容体を介してシグナルが伝達される。神経解剖学の重要な基本概念の一つに、「グルタミン酸作動性の興奮性シナプスはシナプス後部の肥厚が著しい非対称性シナプスで、GABAやグリシン作動性の抑制性シナプスは対称性シナプスである」がある。ところが、NMDA型グルタミン酸受容体のNR3サブユニットは、NR1サブユニットと会合してグリシン作動性の興奮性受容体を形成することが報告された。そこで、本研究では、「興奮性-非対称性シナプス/抑制性-対称性シナプス」の原則が正しいのか、「グルタミン酸-興奮性終末/グリシン-抑制性終末」の原則が正しいのかを明らかにする目的で、NR3サブユニットが分布するシナプスの形態学的特徴と神経回路における局在を検討した。この目的達成のため、NR3Aに対する特異抗体を作成したその結果、NR3Aは、小脳では抑制性ニューロンの樹状突起に選択的に発現し、登上線維との間の対称性シナプスと思われる部位に局在していた。一方、登上線維とプルキンエ細胞との間の非対称性シナプスや、平行線維と抑制性ニューロンとの間の非対称性シナプスには存在しなかった。従って、NR3Aはグルタミン酸を放出する神経終末の対称性シナプスに分布し、いずれの原則にも従わないユニークな発現局在をとることが明らかとなった。

Research Products

• [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)
  • Author(s): Takasaki C, Miura E, Watanabe M
  • Journal Title: Biomed Res (in press)
  • NAID: 130004903731
• [Journal Article] Characterization of a novel low-molecular-mass dual specificity phosphatase-4 (LDP-4) expressed in brain. (2007)
  • Author(s): Takagaki K, Shima H, Tanuma N, Nomura M, Satoh T, Watanabe M, Kikuchi K
  • Journal Title: Mol. Cell. Biochem. (in press)
• [Journal Article] Number and density of AMPA receptors in individual synapses in the cerebellum as revealed by SDS-digested freeze-fracture replica labeling. (2007)
  • Author(s): Masugi-Tokita M, Tarusawa E, Watanabe M, Molnar E, Fujimoto K, Shigemoto R
  • Journal Title: J. Neurosci. (in press)
• [Journal Article] Phospholipase Cβ3 is distributed in both somatodendritic 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: Eur. J. Neurosci. (in press)
• [Journal Article] Diminished climbing fiber innervation of Purkinje cells in the cerebellum of myosin Va mutant mice and rats. (2007)
  • Author(s): Takagishi Y, Hashimoto H, Kayahara T, Watanabe M, Otsuka H, Mizoguchi A, Kano M, Murata Y
  • Journal Title: J. Neurobiol. (in press)
• [Journal Article] Characterization of a transneuronal cytokine family Cbln. regulation of secretion by heteromeric assembly. (2007)
  • Author(s): Iijima T, Miura E, Matsuda K, Kondo T, Kamekawa Y, Watanabe M, Yuzaki M
  • Journal Title: Eur. J. Neurosci. (in press)
• [Journal Article] Ca^<2+> permeability of the channel pore is not essential for the δ2 glutamate receptor to regulate synaptic plasticity and motor coordination. (2007)
  • Author(s): Kakegawa W, Miyazaki T., Hirai H, Motohashi J, Mishina M, Watanabe M, Yuzaki M
  • Journal Title: J. Physiol. (in press)
• [Journal Article] Complementary stripes of phospholipase Cβ3 and Cβ4 expression by Purkinje cell subsets in the mouse cerebellum. (2006)
  • Author(s): Sarna JT, Marzban H, Watanabe M, Hawkes R
  • Journal Title: J. Comp. Neurol. 496 Pages: 303-313
• [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
  • Journal Title: Mol. Cell. Neurosci. 31 Pages: 326-333
• [Journal Article] Improved methods for ultracryotomy of CNS tissue for ultrastructural and immunogold analyses. (2006)
  • Author(s): Akagi T, Ishida K, Hanasaka T, Hayashi S, Watanabe M, Hashikawa T, Tohoyama K
  • Journal Title: J Neurosci. Methods 153 Pages: 276-282
• [Journal Article] The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic site 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: J. Neurosci. 26 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 (Corresponding author)
  • Journal Title: J. Neurochem. 97 Pages: 1431-1446
• [Journal Article] Diacylglycerol kinaseζis involved in the process of cerebral infarction. (2006)
  • Author(s): Nakano T, Hozumi Y, Ali H, Saino-Saito S, Kamii H, Sato S, Kayama T, Watanabe M, Kondo H, Goto K
  • Journal Title: Eur. J. Neurosci. 23 Pages: 1427-1435
• [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)
  • Author(s): Yoshida T, Fukaya M, Uchigashima M, Kamiya H, Kano M, Watanabe M (Corresponding author)
  • Journal Title: J. Neurosci. 26 Pages: 4740-4751
• [Journal Article] Phenotyping of sensory and sympathetic ganglion neurons of a galanin-overexpressing mouse-Possible implications for pain processing. (2006)
  • Author(s): Brumovsky PR, Hygge-Brakeman K, Villar MJ, Watanabe M, Wiesenfeld-Hallin Z, Hokfelt T
  • Journal Title: J. Chem. Neuroanat. 31 Pages: 243-262
• [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)
  • Author(s): Yoshimura K, Shibata M, Koike M, Gotoh K, Fukaya M, Watanabe M, Uchiyama Y
  • 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)
  • Author(s): Sasaki H, Hozumi Y, Hasegawa H, Ito T, Takagi M, Ogino T, Watanabe M, Goto K
  • Journal Title: Cell Tissue Res. 326 Pages: 35-42
• [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
  • Journal Title: EMBO J. 25 Pages: 2867-2877
• [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)
  • Author(s): Moriguchi S, Nishi M, Komazaki S, Sakagami H, Miyazaki T, Masumiya H, Saito S, Watanabe M, Kondo H, Yawo H, Fukunaga K, Takeshima H
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 10811-10816
• [Journal Article] Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family. (2006)
  • Author(s): Kume H, Tohgo A, Kaneko I, Kondo H, Fukunaga K, Kano M, Watanabe M, Takeshima H
  • 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
  • NAID: 120000955769
• [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] Indispensability of glutamate transporter GLAST and GLT1 to brain development. (2006)
  • Author(s): Matsugami TR, Tanemura K, Mieda M, Nakatomi R, Yamada K, Kondo K, Ogawa M, Obata K, Watanabe M, Hashikawa T, Tanaka K
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 12161-12166
• [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
• [Journal Article] Tonic enhancement of endocannabinoid-mediated retrograde suppression of inhibition by cholinergic interneuron activity in the striatum. (2006)
  • Author(s): Narushima M, Uchigashima M, Matsui M, Manabe T, Watanabe M, Kano M
  • Journal Title: J. Neurosci. 27 Pages: 496-506
• [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.
  • Journal Title: Mol.Cell.Neurosci. (in press)
• [Journal Article] Complementary stripes of phospholipase Cβ3 and Cβ4 expression by purkinje cell subsets in the mouse cerebellum. (2006)
  • Author(s): Sarna, J.T., Marzban, H., Watanabe, M., W, Hawkes, R.
  • Journal Title: J.Comp.Neurol. (in press)
• [Journal Article] Improved methods for ultracryotomy of CNS tissue for ultrastructural and immunogold analyses. (2006)
  • Author(s): Akagi, T., Ishida, K., Hanasaka, T., Hayasni, S., Watanabe.M., Hashikawa, T., Tohoyama, K.
  • Journal Title: J.Neurosci.Methods (in press)
• [Journal Article] Maintenance of presynaptic function by AMPA receptor-mediated excitatory postsynaptic activity in adult brain. (2006)
  • Author(s): Kakizawa, S., Miyazaki, T., Iino, M., Watanabe, M., Kano, M.
  • Journal Title: Proc.Natl.Acad.Sci.USA (in press)
• [Journal Article] Rescue of abnbormal phenotypes of the δ2 glutamate receptor-null mice by mutant δ2 transgenes. (2005)
  • Author(s): Hirai, H., Miyazaki, T., Kakegawa, W., Matsuda, S., Mishina, M., Watanabe, M., Yuzaki, M.
  • Journal Title: EMBO report 6 Pages: 90-95
• [Journal Article] Retinotectal transmission in the optic tectum of rainbow trout. (2005)
  • Author(s): Kinoshita, M., Fuyaka, M., Tojima, T., Kojima, S., Ando, H., Watanabe, M., Urano, A., Ito, E.
  • Journal Title: J.Comp.Neurol. 484 Pages: 249-259
• [Journal Article] Evidence for creatine biosynthesis in Muller glia. (2005)
  • Author(s): Nakashima, T., Tomi, M., Tachikawa, M., Watanabe, M., Terasaki, T., Hosoya, K.
  • Journal Title: Glia 52 Pages: 47-52
• [Journal Article] NR2-to-NR3B subunit conversion of NMDA receptor in early postnatal motoneurons. (2005)
  • Author(s): Fukaya, M., Hayashi, Y., Watanabe, M.
  • Journal Title: Eur.J.Neurosci. 21 Pages: 47-52
• [Journal Article] Control of synaptic connection by glutamate receptor δ2 in the mature cerebellum. (2005)
  • Author(s): Takeucni, T., Miyazaki, T., Watanabe, M., Mori, H., Sakimura, K., Mishina, M.
  • Journal Title: J.Neurosci. 25 Pages: 2143-2156
• [Journal Article] Differential roles of glial and neuronal glutamate transporters in Purkinje cell synapses. (2005)
  • Author(s): Takayasu, Y., Iino, M., Kakegawa, W., Maeno, H., Watase, K., Wada, K., Miyazaki, T., Watanabe, M., Tanaka, K., Ozawa, S.
  • Journal Title: J.Neurosci. 25 Pages: 8788-8793
• [Journal Article] Identification and characterization of a novel member of murine semaphorin family. (2005)
  • Author(s): Taniguchi, M., Masuda, T., Fukaya, M., Kataoka, H., Mishina, M., Yaginuma, H., Watanabe, M., Shimizu, T.
  • Journal Title: Genes to Cells 10 Pages: 785-792
• [Journal Article] Ptfla, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. (2005)
  • Author(s): Hoshino, M., Nakamura, S., Mori, K., Kawaucni, T., Terao, M., Nishimura, Y.V., Fukuda, A., Fuse, T., Matsuo, N., Sone, M., Watanabe, M., Bito, H., Terashima, T., Wright, C.V.E., Kawaguchi, Y., Nakao, K., Nabeshima, Y.
  • Journal Title: Neuron 47 Pages: 201-213
• [Journal Article] Distinct spatio-temporal expression of ABCA and ABCG transporters in the developing and adult mouse brain. (2005)
  • Author(s): Tachikawa, M., Watanabe, M., Hori, S., Fukaya, M., Ohtsuki, S., Asashimal, T., Terasaki, T.
  • Journal Title: J.Neurochem. 95 Pages: 294-304
• [Journal Article] Autoantibodies and cell-mediated autoimmunity to NMDA-type GluTe2 in patients with Rasmussen's encephalitis and chronic progressive epilepsia partialis continua. (2005)
  • Author(s): Takahasni, Y., Mori, H., Mishina, M., Watanabe, M., Kondo, N., Shomomura, J., Kubota, Y., Matsuda, K., Fukushima, K., Shiroma, M., Akasaka, N., Nishida, H., Imamura, A., Watanabe H., Sugiyama, N., Ikezawa, M., Fujiwara, T.
  • Journal Title: Epilepsia 46 Pages: 152-158
• [Journal Article] Fyn kinase-mediated phosphorylation of NMDA receptor NR2B subunit at Tyr1472 is essential for maintenance of neuropathic pain. (2005)
  • Author(s): Abe, T., Matsumura, S., Katano, T., Mabuchi, T., Takagi, K., Xu, L., Yamamoto, A., Hattori, K., Yagi, T., Watanabe, M., Nakazawa, T., Yamamoto, T., Mishina, M., Nakai, Y., Ito, S.
  • Journal Title: Eur.J.Nerosci. 22 Pages: 1445-1455
• [Journal Article] Target-cell-specific left-right asymmetry of NMDA receptor content in Schaffer collateral synapses in ε1/NK2A knock-out mice. (2005)
  • Author(s): Wu, Y., Kawakami, R., Fukaya, M., Sakimura, K., Mishina, M., Watanabe, M., Ito, I., Shigemoto, R.
  • Journal Title: J.Neurosci. 25 Pages: 9213-9226
• [Journal Article] Spatial diversity in gene expression for VDCCγ subunit family in developing and adult mouse brains. (2005)
  • Author(s): Fukaya, M., Yamazaki, M., Sakimura, K., Watanabe, M.
  • Journal Title: Neurosci.Res. 53 Pages: 376-383
  • NAID: 10017131285
• [Journal Article] Complementary roles of cholecystokinin and parvalbumin expressing GABAergic neurons in hippocampal network oscillations. (2005)
  • Author(s): Klausberger, T., Marton, L.F., O'Neill, J., Huck, J.H.J., Dalezios, Y., Fuentealba, P., Suen, W.-Y., Papp, E., Kaneko, T., Watanabe, M., JCsicsvari, J., Somogyi, P.
  • Journal Title: J.Neurosci. 25 Pages: 9782-9793
• [Journal Article] Clbn1 is essential for synaptic integrity and information processing in the cerebellum. (2005)
  • Author(s): Hirai, H., Pang, Z., Bao, D., Miyazaki, T., Li, X., Parris, J., Rong, Y., Watanabe, M., Yuzaki, M., Morgan, J.I.
  • Journal Title: Nature Neurosci. 8 Pages: 1534-1541
• [Journal Article] Cellular distribution of glutamate transporters in the gastrointestinal tract of mice. An immunohistochemical and in situ hybridization approach. (2005)
  • Author(s): Iwanaga, T., Goto, M., Watanabe, M.
  • Journal Title: Biomed.Res. 26 Pages: 271-278
  • NAID: 130004903697