糖鎖生物学と神経科学の融合による神経糖鎖生物学領域の創成

Establishment of Neuroglycobiol ogy (Glycobiological Approach for Neuroscience)

研究課題番号:16GS0313

2008年度 研究成果報告書 PDF

代表者

    • 岡 昌吾
    • OKA, Shogo
    • 研究者番号:60233300
    • 京都大学・医学研究科・教授

研究課題基本情報

  • 研究期間

    2004年度〜2008年度

  • 研究分野

  • 審査区分

  • 研究種目

    学術創成研究費

  • 研究機関

    京都大学

  • 配分額

    • 2004年度:107900千円 (直接経費:83000千円, 間接経費:24900千円)
    • 2005年度:104520千円 (直接経費:80400千円, 間接経費:24120千円)
    • 2006年度:101400千円 (直接経費:78000千円, 間接経費:23400千円)
    • 2007年度:100750千円 (直接経費:77500千円, 間接経費:23250千円)
    • 2008年度:101400千円 (直接経費:78000千円, 間接経費:23400千円)

研究分担者等

研究分担者

    • MA, BRUCE
    • 研究者番号:00378788
    • 立命館大学・COE推進機構・准教授
    • 小堤 保則
    • KOZUTSUMI, Yasunori
    • 研究者番号:70205425
    • 京都大学・生命科学研究科・教授
    • 木下 政人
    • KINOSITA, Masato
    • 研究者番号:60263125
    • 京都大学・農学研究科・助教

    • 川崎 ナナ
    • KAWASAKI, Nana
    • 研究者番号:20186167
    • 国立薬品食品衛生研究所・生物薬品部・室長
    • 石 龍徳
    • SEKI, Tatsunori
    • 研究者番号:20175417
    • 東北大学・医学研究科・准教授

連携研究者

    • 伊藤 信行
    • ITOH, Nobuyuki
    • 研究者番号:10110610
    • 京都大学・薬学研究科・教授

研究概要

生物はタンパク質だけでなく糖鎖にもその生体情報を書き込み、同一タンパク質に多様な機能を付加していると考えられる。神経発生、神経回路形成は細胞の分化、移動、軸索の伸長、標的細胞の認識、シナプス形成など多くの過程を経て行われる。これらの過程において特徴的な発現を示す糖鎖について研究を行い、糖鎖が神経発生、神経可塑性において重要な役割を担っていること示す知見を得た。

発表文献

雑誌論文

  • D. Anzai, Y. Tonoyama, A. Ikeda, T. Kawasaki and S. Oka: "Regulated expression of HNK-1 carbohydrate is essential for medaka (Oryzias latipes) embryogenesis" Glycobiology (in press). (2009), 1

  • Y. Tonoyama, D. Anzai, A. Ikeda, S. Kakuda, M. Kinoshita, T. Kawasaki, S. Oka: "Essential role of beta 1,4-galactosyltransferase 2 during medaka (Oryzias latipes) gastrulation" Mech. Dev (in press). (2009), 1

  • T. Yoshihara, K. Sugihara, Y. Kizuka, S. Oka and M. Asano: "Learning/memory impairment and reduced expression of the HNK-1 carbohydrate in beta 4-galactosyltransferase-II-deficient mice" J. Biol. Chem 284 (18). 12550-12561 (2009), 1

  • Y. Kizuka, Y. Tonoyama and S. Oka: "Distinct transport and intracellular activities of two GlcAT-P isoforms" J. Biol. Chem 284(14). 9247-9256 (2009), 1,

  • N. Kawasaki, CW. Lin CW, R. Inoue, KH. Khoo, N. Kawasaki, BY. Ma, S. Oka, M. Ishiguro, T. Sawada, H. Ishida, T. Hashimoto and T. Kawasaki: "Highly Fucosylated N-Glycan Ligands for Mannan-binding Protein Expressed Specifically on CD26 (DPPVI) Isolated from a Human Colorectal Carcinoma Cell Line" SW1116. Glycobiology 19(4). 437-450 (2009), 1

  • E. Shimada, M. Kinoshita and K. Murata: "Expression of cardiac myosin light chain 2 (mcmlc2) during embryonic heart development in medaka fish, Oryzias latipes, and phylogenetic relationship with other myosin light chains" Develop. Growth Differ 51. 1-16 (2009), 1,

  • H. Yagi, K. Yamada, E. Ohno, M. Utsumi, Y. Yamaguchi, E. Kurimoto, N. Takahashi N, S. Oka, T. Kawasaki and K. Kato: "Development and application of high performance liquid chromatography map of glucuronyl N-glycans" Open Glycoscience 1. 8-18 (2008), 1,

  • I. Morita, Y. Kizuka, S. Kakuda and S. Oka: "Expression and function of the HNK-1 carbohydrate" J. Biochem 43. 719-724 (2008), 1,

  • Y. Kizuka, K. Kobayashi, S. Kakuda, Y. Nakajima, S. Itoh, N. Kawasaki and S. Oka: "Laminin-1 is a novel carrier glycoprotein for the non-sulfated HNK-1 epitope in mouse kidney" Glycobiology 18. 331-338 (2008), 1,

  • A. Burgess, SR. Wainwright, LS. Shihabuddin, U. Rutishauser, T. Seki and I.. Aubert: "Polysialic acid regulates the clustering, migration, and neuronal differentiation of progenitor cells in the adult hippocampus" Develop Neurobiol 68. 1580-1590 (2008), 1,

  • S. Itoh, A. Hachisuka, N. Kawasaki, N. Hashii, R. Teshima, T. Hayakawa, T. Kawanishi and T. Yamaguchi: "Glycosylation analysis of IgLON family proteins in rat brain by liquid chromatography/multiple-stage mass spectrometry" Biochemistry 47. 10132-10154 (2008), 1,

  • M. Inoue, K. Kato, H. Matsuhashi, Y. Kizuka, T. Kawasaki and S. Oka: "Distributions of glucuronyltransferases, GlcAT-P and GlcAT-S, and their target substrate, the HNK-1 carbohydrate epitope in the adult mouse brain with or without a targeted deletion of the GlcAT-P gene" Brain Res 1179. 1-15 (2007), 1

  • BY. Ma, N. Nakamura, V. Dlabac, H. Naito, S. Yamaguchi, M. Ishikawa, M. Nonaka, M. Ishiguro, N. Kawasaki, S. Oka and T. Kawasaki: "Isolation, cloning, and characterization of a novel phosphomannan-binding lectin from porcine serum" J. Biol. Chem 282 (17). 12963-75 (2007), 1

  • BY. Ma, M. Kaihama, M. Nonaka, S. Oka, N. Kawasaki and T. Kawasaki: "LPS suppresses expression of asialoglycoprotein-binding protein through TLR4 in thioglycolate-elicited peritoneal macrophages" Glycoconj. J 24. 243-249 (2007), 1

  • T. Seki, T. Namba, H. Mochizuki and M. Onodera: "Clustering, migration and neurite formation of neural precursor cells in the adult rat hippocampus" J Comp Neurol 502. 275-290 (2007), 1,

  • H. Yamamoto, H. Takematsu, R. Fujinawa, Y. Naito, Y. Okuno, G. Tsujimoto, A. Suzuki and Y. Kozutsumi: "Correlation Index-Based Responsible-Enzyme Gene Screening (CIRES), a Novel DNA Microarray-Based Method for Enzyme Gene Involved in Glycan Biosynthesis" PLoS ONE 2. e1232 (2007), 1

  • Y. Naito, H. Takematsu, S. Koyama, S. Miyake, H. Yamamoto, R. Fujinawa, M. Sugai, Y. Okuno, G. Tsujimoto, T. Yamaji, Y. Hashimoto, S. Itohara, T. Kawasaki, A. Suzuki and Y. Kozutsumi: "Germinal center marker GL7 probes activation-dependent repression of N-glycolylneuraminic acid, a sialic acid species involved in the negative modulation of B-cell activation" Mol. Cell Biol 27. 3008-3022 (2007), 1

  • N. Koike, Y. Kassai, Y. Kouta, H. Miwa, M. Konishi and N. Itoh: "Brorin a novel secreted BMP antagonist, promotes neurogenesis in mouse neural precursor cells" J. Biol. Chem 282. 15843-15850 (2007), 1

  • T. Shiba, S. Kakuda, M. Ishiguro, I. Morita, S. Oka, T. Kawasaki, S. Wakatsuki and R. Kato: "Crystal structure of GlcAT-S, a human glucuronyltransferase, involved in the biosynthesis of the HNK-1 carbohydrate epitope" Proteins 65 (2). 499-508 (2006), 1

  • Y. Kizuka, T. Matsui, H. Takematsu, Y. Kozutsumi, T. Kawasaki and S. Oka: "Physical and functional association of glucuronyltransferases and sulfotransferase glucuronyltransferases and sulfotransferase involved in HNK-1 biosynthesis" J. Biol. Chem. 281(19). 13644-13651 (2006), 1,

  • S. Itoh, N. Kawasaki, N. Hashii, A. Harazono, Y. Matsuishi, T. Kawanishi and T. Hayakawa: "N-linked oligosaccharide analysis by liquid chromatography with graphitized carbon column/ liner ion trap-Fourier transform ion cyclotron resonance mass spectrometry in positive and negative ion modes" J. Chromatogr. A 1103. 296-306 (2006), 1

  • M. Hirano, BY. Ma, N. Kawasaki, K. Okimura, M. Baba, T. Nakagawa, K. Miwa, N. Kawasaki, S. Oka and T. Kawasaki: "Mannan-binding protein blocks the activation of metalloproteases meprin alpha and beta" J. Immunology 175 (5). 3177-3185 (2005), 1

  • H. Tagawa, Y. Kizuka, T. Ikeda, S. Itoh, N. Kawasaki, H. Kurihara, M. L. Onozato, A. Tojo, T. Sakai, T. Kawasaki and S. Oka: "Non-sulfated form of the HNK-1 carbohydrate is expressed in mouse kidney" J. Biol. Chem 280 (25). 23876-23883 (2005), 1,

  • M.Terada, K.H. Khoo, R. Inoue, C.I. Chen, K. Yamada, H. Sakaguchi, N. Kadowaki, BY. Ma, S. Oka, T. Kawasaki and N. Kawasaki: "Characterization of oligosaccharide ligands expressed on SW1116 cells recognized by Mannan-binding protein a highly fucosylated polylactosamine type N-glycan" J. Biol. Chem. 280 (12). 10897-10913 (2005), 1

  • S. Kakuda, Y. Sato, Y. Tonoyama, S. Oka and T. Kawasaki: "Different acceptor specificities of two glucuronyltransferases involved in the biosynthesis of HNK-1 carbohydrate" Glycobiology 15 (2). 203-210 (2005), 1

  • A. Miyake, Y. Nakayama, M. Konishi and N. Itoh: "Fgf19 regulated by Hh signaling is required for zebrafish forebrain development" Dev. Biol 228. 259-275 (2005), 1,

  • K. Uemura, H. Yamamoto, T. Nakagawa, K. Nakamura, N. Kawasaki, S. Oka, B.Y. Ma and T. Kawasaki: "Superoxide production from human polymorphonuclear leukocytes by human mannan-binding protein (MBP)" Glycoconj J 21. 79-84 (2004), 1,

  • S. Kakuda, T. Shiba, M. Ishiguro, H. Tagawa, S. Oka, Y. Kajiwara, T. Kawasaki, S. Wakatsuki and R. Kato: "Structural basis for acceptor substrate recognition of a human glucuronyltransferase, GlcAT-P, an enzyme critical in the biosynthesis of the carbohydrate epitope HNK-1" J Biol Chem 279. 22693-22703 (2004), 1

  • S. Kakuda, S. Oka, T. Kawasaki: "Purification and characterization of two recombinant human glucuronyltransferases involved in the biosynthesis of HNK-1 carbohydrate in Escherichia coli" Protein Expr Purif 35. 111-119 (2004), 1,

学会発表

  • Y. Kizuka, Y. Tonoyama, S. Oka: "Two GlcAT-P isoforms are distinctly transported in cell. Clinical and Translational Research on Cancer" Glycomics Applications. (20090326). 伊勢

  • D. Anzai, Y. Tonoyama, E. Tane, S. Oka: "The functional analysis of HNK-1 carbohydrate in medaka embryogenesis Joint meeting of the Socie'te' France de Biologie du De'velopment" Japanese Society of Developmental Biologists. (20080913-17). フランスGiens

  • 木塚康彦、竹内祐介、森田一平、角田品子、岡昌吾: "糖転移酵素GlcAT-Pの細胞質領域による分泌制御と活性調節" 第28回日本糖質学会. (20080820). つくば

  • 岡昌吾: "スパイン形成におけるHNK-1糖鎖の役割" 第31 回日本神経科学学会. (20080710). 東京

  • 殿山泰弘、安西大輔、池田篤史、角田品子、木下政人、川崎敏祐、岡昌吾: "Beta1,4-galactosyltransferase 2 is required for convergence and extension movements during medaka (Oryzias latipes) gastrulation" 第41回日本発生生物学会(国際発生生物学会と合同). (20080528). 徳島

  • 山下彩貴、木塚康彦、角田品子、岡昌吾: "GlcAT-P遺伝子欠損マウスにおける残存HNK-1糖鎖発現に関する研究" 糖鎖発現に関する研究第128年回日本薬学会. (20080326-28). 横浜

  • 岡昌吾: "発生過程に重要な糖鎖の機能解" 第128年回日本薬学会. (20080326-28). 横浜

  • 岡昌吾: "神経機能に重要なHNK-1糖鎖BMB2007" 第30回日本分子生物学会年会、第80回日本生化学会大会合同大会. (20071211-15). 横浜

  • 岡昌吾: "神経可塑性とHNK-1糖鎖" 第5回糖鎖科学コンソーシアムシンポジウム. (20071126-27). 東京

  • Y. Kizuka, N. Kawasaki, N. Maeda, T. Kawasaki and S. Oka: "Characterization of a unique HNK-1 (Human Natural Killer-1) carbohydrate on phosphacan in mouse brain. Glyco19" XIX International Symposium on Glycoconjugates. (20070715-20). Cairns, Australia

  • Y. Tonoyama, D. Anzai, A. Ikeda, S. Kakuda, M. Kinoshita, T. Kawasaki, S. Oka: "Essential role of beta1,4-galactosyltransferase 2 in convergence and extension movements during medaka (Oryzias latipes) embryogenesi" HUPO 6th annual world congress. (20071006-10). Seoul, Korea

  • 岡昌吾: "神経可塑性におけるHNK-1糖鎖の役割" 日本薬学会第127年会. (20070300). 富山

  • 岡昌吾: "HNK-1糖鎖の機能" 第4回糖鎖科学コンソーシアムシンポジウム. (20061023-24). 東京

  • 小林恭子, 陣内俊和, 角田品子, 木塚康彦, 高橋智, 川崎敏祐, 岡昌吾: "HNK-1糖鎖生合成酵素GlcAT-S遺伝子欠損マウスの作成とその生化学的解釈" 第26回日本糖質学会年会. (20060823-25). 仙台

  • S. Oka, Y. Kizuka, S. Kakuda, I. Morita, S. Yamamoto and T. Kawasaki: "Function and Regulation of the HNK-1 Carbohydrate in the Nervous System" GlycoT 2006 5^<th> International Symposium on Glycosyltransferases. (20060625-28). Tsukuba(Japan)

  • I. Morita, T. Shiba, S. Kakuda, S. Oka, T. Kawasaki, S. Watatsuki, R. Kato: "Structural and Biochemical Studies on Human Glucuronyltransferase, GlcAT-S" Involved in the Biosynthesis of the Carbohydrate HNK-1.20^<th> IUBMB Inteanational Congress of Biochemistry and Molecular Biology and 11^<th> FAOBMB Congress. (20060618-23). Kyoto(Japan)

  • Y. Kizuka, N. Maeda, N. Kawasaki, T. Kawasaki, S. Oka: "A unique type of HNK-1 carbohydrate expressed on phosphacan is biosynthesized by GlcAT-P" 20^<th> IUBMB Inteanational Congress of Biochemistry and Molecular Biology and 11^<th> FAOBMB Congress. (20060618-23). Kyoto(Japan)

  • 殿山泰弘, 安西大輔, 大上志穂, 川崎敏祐, 岡昌吾: "メダカ胚発生に関わる糖転移酵素B4GALT2 の機能解析" 日本発生生物学会第39回大会. (20060531-0603). 広島

  • 安西大輔, 殿山泰弘, 大上志穂, 川崎敏祐, 岡昌吾: "メダカを用いたHNK-1糖鎖の機能解析" 日本発生生物学会第39回大会. (20060531-0603). 広島

  • 岡昌吾: "メダカの発生における糖鎖の重要性" 第28回日本分子生物学会. (20051200). 福岡

  • S. Oka, H. Tagawa, Y. Kizuka, N. Kawasaki, H. Kurihara and T. Kawasaki: "Expression of the non-sulfated HNK-1 carbohydrate in mouse kidney" Pacifichem 2005. (20051200). Honolulu, Hawaii

  • Y. Tonoyama, D. Anzai, S. Ogami and S. Oka: "A traial with medaka (oryzias latipes) to analyze the function of glycans involved in the embryogenesis" 2nd Soul-Osaka-Kyoto Joint Symosium on Pharmaceutical Sciences. (20051205-06). Osaka

図書

  • Y. Tonoyama and S. Oka: "Cell trace experiment with a caged fluorescent dye during medaka gastrulation in Medaka: Biology, Management, and Experimental Protocols. (M. Kinoshita, K. Murata, K. Naruse, M. Tanaka, Eds)" Wiley-Blackwell. (in press) (2009)

  • S. Kakuda, T. Kawasaki and S. Oka: "Glucuronyltransferases Involved in the HNK-1 Biosynthesis. in Experimental Glycoscience-Glycobiology (N. Taniguchi, A. Suzuki, Y. Ito, H. Narimatsu, T. Kawasaki, and S. Hase, Eds)" Springer. pp47-49 (2008),

  • Y. Kizuka and S. Oka: "Functional Roles of the HNK-1 Carbohydrate and Polysialic Acid in the Nervous System. in Experimental Glycoscience-Glycobiology (N. Taniguchi, A. Suzuki, Y. Ito, H. Narimatsu, T. Kawasaki, and S. Hase, Eds)" Springer. 180-181 (2008)

  • I. Morita and S. Oka: "Glucuronyltransferase (GlcAT-P) Gene-Deficient Mice. In Experimental Glycoscience-Glycobiology (N. Taniguchi, A. Suzuki, Y. Ito, H. Narimatsu, T. Kawasaki, and S. Hase, Eds)" Springer. 381-382 (2008),

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