Mechanisms for molecular cluster formation and specificity in the bio-regulation with glycosphingolipids

• Project/Area Number: 19390086
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: FURUKAWA Koichi Nagoya University, 大学院・医学系研究科, ・教授 (80211530)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: 糖脂質 / ガングリオシド / スフィンゴ糖脂質 / 分子クラスター / 神経変性 / 補体 / ミクロドメイン / ラフト / ニューロン / グリア / サイトカイン / ノックアウト / GM3

Research Abstract

スフィンゴ糖脂質による生体調節、とくに分子クラスターの形成プロセスとシグナルの調節機構に関し多くの成果が得られた。糖脂質の欠損では、残存糖脂質構造の代償機能が働く。GM3-only マウスの解析から、細胞膜ミクロドメインの健常性の維持にとって、糖脂質糖鎖の正しい構成が必須であることが、種々の実験から明らかになった。とくに、ラフトの異常が補体系の活性化を惹起して、神経変性の重要な要因となることが示唆された。

Research Products

• [Journal Article] Neuromuscular synaptic transmission in aged ganglioside-deficient mice (2009)
  • Author(s): Zitman, F.M., Todorov, B., Verschuuren, J.J., Jacobs, B.C., Furukawa, K., Furukawa, K., Willison, H.J.,
  • Journal Title: Neurobiology of Aging (in press)
• [Journal Article] Barnett, S.C. In vitro analysis of glial cell function in ganglioside deficient mice (2009)
  • Author(s): Silajdzic, E, Willison, H.J, Furukawa, K.
  • Journal Title: J. Neurosci. Res. (In press)
• [Journal Article] Gangliosides determine the amyloid pathology of Alzheimer disease (2009)
  • Author(s): Oikawa, N, Yamaguchi, H, Ogino, K., Taki, T, Yuyama, K, Yamamoto, N, Shin, R.-W, Furukawa, K, and Yanagisawa K.
  • Journal Title: Neuroreport (in press)
• [Journal Article] The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice (2009)
  • Author(s): Greenshields, K.N, Halstead, S.K, Zitman, F.M, Rinaldi, S, Brennan, K.M, O'Leary, C, hamberlain, L.H, Easton, A, Roxburgh, J, Pediani, J, Furukawa, K, Furukawa, K, Goodyear, C.S, Plomp, J.J, Willison, H.J.
  • Journal Title: J. Clin. Invest. (in press)
• [Journal Article] Reduced motor and sensory functions and emotional response in GM3-only mice: emergence from early stage of life and exacerbation with aging (2009)
  • Author(s): Orie Tajima, Nobuaki Egashira, Yuhsuke Ohmi, Yoshihiko Fukue, Kenichi Mishima, Katsunori Iwasaki, Michihiro Fujiwara, Yasuo Sugiura, Keiko Furukawa, Koichi Furukawa
  • Journal Title: Behavioural Brain Research (in press)
• [Journal Article] Neuromuscular synaptic function in mice lacking major subsets of gangliosides (2009)
  • Author(s): Zitman, F.M., Todorov, B., Jacobs, B.C., Verschuuren, J.J., Furukawa, K., Furukawa, K., Willison, H.J., and Plomp, J.J.
  • Journal Title: Neuroscience (in press)
• [Journal Article] Glycoconjugate glycosyltransferases (2009)
  • Author(s): Koichi Furukawa, Akiko Tsuchida, Tetsuya Okajima, Keiko Furukawa
  • Journal Title: Glycoconj. J. (in press)
• [Journal Article] Reduced motor and sensory functions and emotional response in GM3-only mice : emergence from early stage of life and exacerbation with aging. (2009)
  • Author(s): Tajima, O., Egashira, N., ., et al.
  • Journal Title: Behavioural Brain Research (in press)
  • Peer Reviewed
• [Journal Article] The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice (2009)
  • Author(s): Greenshields KN, Halstead SK., et al.
  • Journal Title: J. Clin. Invest. (in press)
  • Peer Reviewed
• [Journal Article] O-linked N-acetylglucosamine is present on the extracellular domain of notch receptors. (2008)
  • Author(s): Matsuura, A., Ito, M., Sakaidani, Y., Kondo, T., Murakami, K., Furukawa, K., Nadano, D., Matsuda, T. and Okajima, T
  • Journal Title: J. Biol. Chem. 283
• [Journal Article] TRP channels and ASICs mediate mechanical hyperalgesia in models if infmammatory muscle pain and delayed onset muscle soreness (2008)
  • Author(s): Fujii, Y., Ozaki, N., Taguchi, T., Mizumura, K., Furukawa, K., and Sugiura, Y.
  • Journal Title: Pain 140 Pages: 292-304
• [Journal Article] Molecules in the signaling pathway activated by gangliosides can be targets of therapeutics for malignant melanomas (2008)
  • Author(s): Furukawa, K., Hamamura, K., Nakashima, H., Furukawa, K.
  • Journal Title: Proteomics 8 Pages: 3312-3316
• [Journal Article] Roles of complex gangliosides in the development of experimental autoimmune encephalomyelitis (2008)
  • Author(s): Miyamoto K, Takada K, Furukawa K, Furukawa K, Kusunoki S
  • Journal Title: Glycobiology 18 Pages: 408-413
• [Journal Article] Impaired hypoglossal nerve regeneration in complex ganglioside lacking mutant mice: down-regulation of neurotrophic factors and receptors as possible mechanisms (2008)
  • Author(s): Kittaka, D., Itoh, M., Ohmi, Y., Kondo, Y., Fukumoto, S., Urano, T., Tajima, O., Furukawa, K., and Furukawa, K.
  • Journal Title: Glycobiology 18 Pages: 509-516
• [Journal Article] Disruption of GM2/GD2 synthase gene resulted in neo-expression of 9-O-acetyl GD3 irrespective of Tis21 (2008)
  • Author(s): Furukawa, K., Aixinjueluo, W., Kasama, T., Ohkawa, Y., Yoshihara, M., Ohmi, Y., Tajima, O., Suzumura, A., Kittaka, D., and Furukawa, K
  • Journal Title: J. Neurochem 105 Pages: 1057-1066
• [Journal Article] Gene silencing in cancer by histone H3 lysine 27 tri-methylation independent of promoter DNA methylation (2008)
  • Author(s): Yutaka Kondo, Lanlan Shen, Alfred Cheng, Saira Ahmed1, Yanis Boumber, Chantale Charo, Tadanori Yamochi, Takeshi Urano, Koichi Furukawa, Bernard Kwabi-Addo, David L Gold, Yoshitaka Sekido, Tim Hui-Ming Huang and Jean-Pierre J Issa
  • Journal Title: Nat. Genet 40 Pages: 741-750
• [Journal Article] Focal adhesion kinase as well as p130Cas and paxillin is crucially involved in the enhanced malignant properties under expression of ganglioside GD3 in melanoma cells (2008)
  • Author(s): Hamamura, K., Tsuji, M., Nakashima, H., Miyazaki, S., Urano, T., Yamamoto, N., Ueda, M., Furukawa, K., and Furukawa, K.
  • Journal Title: Biochim. Biophys. Acta 1780 Pages: 513-519
• [Journal Article] Disruption of GM2/GD2 synthase gene resulted in neo-expression of 9-0-acetyl GD3 irrespective of Tis21. (2008)
  • Author(s): Furukawa, K., Aixinjueluo, W., et al.
  • Journal Title: J. Neurochen. 105 Pages: 1057-1066
  • Peer Reviewed
• [Journal Article] Disruption of GM2/GD2 synthase gene resulted in overt-expression of 9-O-acetyl GD3 irrespective of Tis21. (2008)
  • Author(s): Furukawa, K., et. al.
  • Journal Title: J. Neurochem. (In press)
  • Peer Reviewed
• [Journal Article] Impaired hypoglossal nerve regeneration in complex ganglioside-lacking mutant mice.: down-regulation of neurotrophic factors and receptors as possible mechanisms. (2008)
  • Author(s): Kittaka, D., et. al.
  • Journal Title: Glycobiology (In press)
  • Peer Reviewed
• [Journal Article] Gangliosides GM1 and GM3 in the living cell membrane form clusters susceptible to cholesterol depletion and chilling (2007)
  • Author(s): Fujita A, Cheng J, Hirakawa M, Furukawa K, Kusunoki S, Fujimoto T.
  • Journal Title: Mol. Biol. Cell 18 Pages: 2112-2122
• [Journal Article] Plasma membrane rafts complete cholesterol synthesis by participating in retrograde movement of precursor sterols (2007)
  • Author(s): Yamauchi Y, Reid PC, Sperry JB, Furukawa K, Takeya M, Chang CC, Chang TY.
  • Journal Title: J. Biol. Chem. 282 Pages: 34994-35004
• [Journal Article] Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers (2007)
  • Author(s): Susuki, K., Baba, H., Tohyama, K., Kanai, K., Kuwabara, S., Hirata, K, Furukawa, K., Furukawa, K., Rasband, M.N., Yuki, N.
  • Journal Title: Glia 55 Pages: 746-757
• [Journal Article] Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: Down-regulation of ST6GalNAc VI in renal cancers (2007)
  • Author(s): Senda, M., Ito, A., Tsuchida, A., Nakamura, Y., Kasama, K., Kiso, M., Katagiri, Y., Yoshikawa, K., Ono, Y., Ogiso, M., Urano, T., Furukawa, K., Oshima, S., and Furukawa, K.
  • Journal Title: Biochem. J. 402 Pages: 459-470
• [Journal Article] Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers. (2007)
  • Author(s): Suzuki, K., et. al.
  • Journal Title: Glia 55 Pages: 746-757
  • Peer Reviewed
• [Presentation] 糖鎖欠損マウスにおける神経再生分子群の探索:Ninjurin2の神経機能制御メカニズム (2008)
  • Author(s): 田島織絵、大海雄介、大川祐樹、古川圭子、古川鋼一
  • Organizer: 第31回日本分子生物学会年会/第81回日本生化学会大会シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 脂質ラフト構築におけるガングリオシドの役割 (2008)
  • Author(s): 大海雄介、田島織絵、大川祐樹、森敦史、稲垣邦江、古川圭子、古川鋼一
  • Organizer: 第31回日本分子生物学会年会/第81回日本生化学会大会シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] 糖脂質を含む複合体形成とシグナル制御 (2008)
  • Author(s): 古川鋼一、大海雄介、大川祐樹、近藤裕史、章青、古川圭子
  • Organizer: 第31回日本分子生物学会年会/第81回日本生化学会大会シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] GM1合成酵を導入したメラノーマ細胞株におけるガングリオシドの分布と細胞表現型の変化 (2008)
  • Author(s): .董宇、章青、近藤裕史、徳田典代、中島英行、田島織絵、古川圭子、古川鋼一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Glycobiology and Search of Biomarkers toward Cancer(癌の攻略に向けた糖鎖研究とバイオマーカー探索)オーガナイザー (2008)
  • Author(s): 成松 久、古川鋼一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 癌関連抗原によるシグナル制御機構と治療応用 (2008)
  • Author(s): 古川鋼一、大川祐樹、浜村和紀、牧野勇介、古川圭子
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Integrin-mediated signaling is essential in the malignant properties of human melanomas enhanced with GD3 expression (2008)
  • Author(s): 大川祐樹、宮崎清香、浜村和紀、宮田麻衣子、大海雄介、田島織絵、古川鋼一、古川圭子
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] ヒトメラノーマ細胞におけるシアリダーゼNeus3の癌性形質への関与 (2008)
  • Author(s): 古川圭子、田島織絵、神戸真理子、宮田麻衣子、宮城妙子、古川鋼一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-25
• [Presentation] GD3発現により活性化されるアダプター分子を標的としたメラノーマのRNAi治療の検討 (2008)
  • Author(s): 牧野勇介、浜村和紀、辻桃子、中島英行、古川圭子、古川鋼一
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-19
• [Presentation] 脂質ラフトを介するシグナル制御と糖脂質糖鎮 (2008)
  • Author(s): 古川鋼一、山内祥生、 浜村和紀、章青、大海雄介、愛新覚羅維、古川圭子
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
  • Year and Date: 2008-05-17
• [Presentation] Novel mechanisms for the neurodegeneration in the mutant mice lacking gangliosides (2008)
  • Author(s): Koichi Furukawa
  • Organizer: Gordon Research Conferences Glicolipids and Sphingolipids
  • Place of Presentation: II ciocco (Italia)
  • Year and Date: 2008-02-21
• [Presentation] Novel mechanisms for the neurodegeneration in the mutant mice lacking gangliosides (2008)
  • Author(s): Koichi Furukawa
  • Organizer: Gordon Reserch Conferences Glycolipid & sphingolipid Biology
  • Place of Presentation: Lucca, Italy
  • Year and Date: 2008-02-20
• [Presentation] 糖鎖をターゲットにした癌治療の試み。研究成果公開シンポジウム (2008)
  • Author(s): 古川鋼一
  • Organizer: 第3の生命鎖 : 糖鎖の謎が今、解る
  • Place of Presentation: 東京
  • Year and Date: 2008-01-25
• [Presentation] Ganglioside GD3 enhences integrins function in human malignant melanomas (2007)
  • Author(s): 大川祐樹、宮崎清香、浜村和紀、宮田麻衣子、田島織絵、浦野健、古川鋼一、古川圭子
  • Organizer: 第30回日本分子生物学会年会/第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] Distribution and compositin of gangliosides in GEM(Glycolipid-Enriched Microdomains)/raft Comparison between a amelanoma cell line and GM1 synthase-trasnfectants (2007)
  • Author(s): Y. Dong, Q. Zhang, Y. Kondo, Y. Zhu, N. Tokuda, H. Nakashima, O. Tajima, K. Furukawa, K. Furukawa
  • Organizer: 第30回日本分子生物学会年会/第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] ヒトメラノーマにおけるNeus3過剰発現の効果 (2007)
  • Author(s): 古川圭子、田島織絵、神戸真理子、古川鋼一、森谷節子、宮城妙子
  • Organizer: 第30回日本分子生物学会年会/第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] Identification of neuronal degeneration- and regeneration-related molecules using GM3 only mice: role of an adhehesion molecule Ninjurin2 in nervous systems (2007)
  • Author(s): O. Tajima, Y. Ohmi, Y. Ohkawa, K. Furukawa, K. Furukawa
  • Organizer: 第30回日本分子生物学会年会/第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] Molecular complez formation based on glycosphingolipids as a functional platform to suport cancer cells (2007)
  • Author(s): 古川鋼一、宮崎清香、辻桃子、大川祐樹、土田明子、古川圭子
  • Organizer: 第30回日本分子生物学会年会/第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] 糖鎖による分子複合体形成のダイナミクス・その制御と破綻 (2007)
  • Author(s): 遠藤玉夫, 古川鋼一
  • Organizer: 第30回日本分子生物学会年会/第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] GM3 only miceの神経変性における補体系の役割 (2007)
  • Author(s): 大海雄介、田島織絵、大川祐樹、古川圭子、古川鋼一
  • Organizer: 第30回日本分子生物学会年会/第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] Involvement of integrins in the malignant phenotypes of human melanomas enhanced by ganglioside GD3 (2007)
  • Author(s): 大川祐樹、宮崎清香、浜村和紀、宮田麻衣子、 田島織絵、浦野健、古川鋼一、古川圭子
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] 酸性糖脂質GD3によるヒトメラノーマの癌性形質形成におけるSrc family kinasesの役割 (2007)
  • Author(s): 古川圭子、辻桃子、浜村和紀、中島英行、古川鋼一
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] 腎癌細胞株における分岐型ジシアリル糖脂質抗原の役割 (2007)
  • Author(s): 土田明子、千田基宏、伊藤明宏、斉藤誠一、木曽真、安藤隆幸、Anne Harduin-Lepers、古川圭子、古川鋼一
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Involvement of beta4GalT-VI in the synthesis of lactosylceramide as analysed by the knockout mice (2007)
  • Author(s): Noriyo Tokuda
  • Organizer: The 21^<st> Century Center of Excellence Program 4^<th> International Symposium on Functional Molecules Linked to Neurodegeneration and Oncogenesis - Towards Molecular Targeted Therapy -
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2007-10-04
• [Presentation] Mechanisms for the enhencement of malignant signals with gangllioside GD3 in human melanoma cells (2007)
  • Author(s): Furukawa K., Hamamura K., Tsuji M., Miyazaki S., Nakashima H., Furukawa K
  • Organizer: 14^<th> European Carbohydrate Symposium
  • Place of Presentation: Lubeck, Germany
  • Year and Date: 2007-09-05
• [Presentation] Roles of complement systems for the nerve degeneration in GM3 only mice (2007)
  • Author(s): Y. Ohmi*, O. Tajima, Y. Ohkawa, K. Furukawa, K. Furukawa
  • Organizer: XIX International Sympojiumu on Glycoconjugates
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2007-07-18
• [Presentation] a : Roles of integrins in the malignant properties of malignant melanomas enhanced by ganglioside GD3 (2007)
  • Author(s): Yuki Ohkawa, Sayaka Miyazaki, Kazunori Hamamura, Maiko Miyata, Koichi FurukawOrie Tajima, Keiko Furukawa
  • Organizer: The 27^<th> Sapporo Cancer Seminar International Symposium
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2007-07-12
• [Book] 糖鎖情報の独自性と普遍性 蛋白質核酸酵素 (2008)
  • Author(s): 古川鋼一, 他(編集)
  • Publisher: 共立出版(東京)(増刊)
• [Book] 糖鎖情報の独自性と普遍性 蛋白質核酸酵素 (2008)
  • Author(s): 古川鋼一, 他編集
  • Publisher: 共立出版(東京)
• [Book] 波及・深化する糖鎖研究 実験医学 (2007)
  • Author(s): 古川鋼一、遠藤玉夫、川崎敏祐(編集)
  • Publisher: 羊土社
• [Book] Biosynthesis of Glycolipids. In Comprehensive glycoscience. From Chemistry to Systems Biology(Eds. By J.P. Kamerling, G.J. Boons, Y.C. Lee, A. Suzuki, N. Taniguchi, A.G.J. Voragen) (2007)
  • Author(s): Furukawa, K., Tsuchida, A., Furukawa, K
  • Publisher: Elsevier, Oxford
• [Book] Knockout mice and glycolipids. In Comprehensive glycoscience. From Chemistry to Systems Biology(Eds. By J.P. Kamerling, G.J. Boons, Y.C. Lee, A. Suzuki, N. Taniguchi, A.G.J. Voragen) (2007)
  • Author(s): Furukawa, K., Tajima, O., Okuda, T., Tokuda, N., and Furukawa, K
  • Publisher: Elsevier, Oxford
• [Book] Knockout mice and glycolipids. In Comprehensive Glycoscience. Article No, : 00086 (2007)
  • Author(s): Furukawa, K., et. al.
  • Total Pages: 800
  • Publisher: Elsevier Ltd
• [Remarks]
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