Analysis of dynamic functions of membrane microdomains by linkage of glycosphingolipids on the cell membrane and transcriptional regulation

• Project/Area Number: 25670141
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Chubu University (2015); Nagoya University (2013-2014)
• Principal Investigator: FURUKWA Koichi 中部大学, 生命健康科学部, 教授 (80211530)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ガングリオシド / 転写因子 / セクレターゼ / ミクロドメイン / 脂質ラフト / メラノーマ / スフィンゴ糖脂質 / 細胞膜 / ネオジェニン / EMARS / 細胞質ドメイン

Outline of Final Research Achievements

Regulatory mechanisms by which interaction between GD3 and its associating molecule, neogenin on the cell surface of melanoma cells were analyzed with focus on the intracytoplasmic domain of neogenin (Ne-ICD). When a protease inhibitor was added to the culture medium, increased levels of Ne-ICD was detected in GD3+ cells, while it was hard to detect when a gamma-secretase inhibitor was added, suggesting that Ne-ICD was generated by recruiting gamma-secretase to lipid rafts by GD3 expression.
By ChIP-sequencing, target genes that are driver by Ne-ICD have been identified, and those genes have been up-regulated by the introduction of Ne-ICD cDNA.

Research Products

• [Journal Article] Regulatory function of glycosphingolipids in the inflammation and degeneration. (2015)
  • Author(s): Furukawa K., Ohmi Y., Kondo Y., Ohkawa Y., Tajima O. and Furukawa K
  • Journal Title: Arch Biochem Biophys Volume: 571 Pages: 58-65
  • DOI: 10.1016/j.abb.2015.02.007
  • Peer Reviewed / Open Access
• [Journal Article] Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with Platelet-derived Growth Factor Receptor α and Yes Kinase. (2015)
  • Author(s): Ohkawa Y, Momota H, Kato A, Hashimoto N, Tsuda Y, Kotani N, Honke K, Suzumura A, Furukawa K, Ohmi Y, Natsume A, Wakabayashi T, Furukawa K.
  • Journal Title: J Biol Chem. Volume: 290 Issue: 26 Pages: 16043-16058
  • DOI: 10.1074/jbc.m114.635755
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impaired O-linked N-acetylglucosaminylation in the endoplasmic reticulum by mutated EGF domain-specific O-linked N-acetylglucosamine transferase found in Adams-Oliver syndrome (2015)
  • Author(s): M.Ogawa, S.Sawaguchi, T.Kawai, D.Nadano, T.Matsuda, H.Yagi, K.Kato, K.Furukawa, and T.Okajima
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 4 Pages: 2137-2149
  • DOI: 10.1074/jbc.m114.598821
  • Peer Reviewed / Open Access
• [Journal Article] b-series gangliosides crucially regulate leptin secretion in adipose tissues. (2015)
  • Author(s): Ji S., Ohkawa Y., Tokizane K., Ohmi Y., Banno R., Furukawa K., Kiyama H. and Furukawa K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 459 Issue: 2 Pages: 189-195
  • DOI: 10.1016/j.bbrc.2015.01.143
  • Peer Reviewed / Open Access
• [Journal Article] Akt-girdin signaling in cancer-associated fibroblasts contributes to tumor progression (2015)
  • Author(s): Yumiko Yamamura, Naoya Asai, Atsushi Enomoto, Takuya Kato, Shinji Mii, Yuji Kondo, Kaori Ushida, Kaoru Niimi, Nobuyuki Tsunoda, Masato Nagino, Shu Ichihara, Koichi Furukawa, Kengo Maeda, Toyoaki Murohara, Masahide Takahashi
  • Journal Title: Cancer Research Volume: 75 Issue: 5 Pages: 813-823
  • DOI: 10.1158/0008-5472.can-14-1317
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ganglioside deficiellcy causes inflammation and neurodegeneration via the activation of complement system in the spinal cord. (2014)
  • Author(s): Yuhsuke Ohmi, Yuki Ohkawa, et al.
  • Journal Title: Journal of Neuroinflammation Volume: 61(印刷中) Issue: 1 Pages: 61-61
  • DOI: 10.1186/1742-2094-11-61
  • Peer Reviewed / Open Access
• [Journal Article] Neuronal Expression of GalNAc Transferase Is Sufficient to Prevent the Age-Related Neurodegenerative Phenotype of Complex Ganglioside-Deficient Mice (2014)
  • Author(s): Denggao Yao, Rhona McGonigal, Jennifer A. Barrie, Joanna Cappell, Madeleine E. Cunningham, Gavin R. Meehan, Simon N. Fewou, Julia M. Edgar, Edward Rowan, Yuhsuke Ohmi, Keiko Furukawa, Koichi Furukawa, Peter J. Brophy, Hugh J. Willison
  • Journal Title: The journal of neuroscience Volume: 34 Issue: 3 Pages: 880-891
  • DOI: 10.1523/jneurosci.3996-13.2014
  • Peer Reviewed / Open Access
• [Journal Article] Neuronal expression of GalNAc transferase is sufficient to prevent the age-related neurodegenerative phenotype of complex ganglioside deficient mice. (2014)
  • Author(s): Yao, D., McGonigal, R., Barrie, J.A., Cappell, J., Cunningham, M.E., Meehan, G.R., Fewou, S.N., Edgar, J.M., Rowan, E., Ohmi, Y., Furukawa, K., Furukawa, K., Brophy, P.J., Willison, H.J.
  • Journal Title: J. Neurosci. Volume: 34 Pages: 880-891
  • Peer Reviewed
• [Journal Article] β4GalT6 is involved in the synthesis of lactosylceramide with less intensity than β4GalT5 (2013)
  • Author(s): Tokuda N, Numata S, Li X, Nomura T, Takizawa M, Kondo Y, Yamashita Y, Hashimoto N, Kiyono T, Urano T, Furukawa K, Furukawa K
  • Journal Title: Glycobiology Volume: 23 Issue: 10 Pages: 1175-1183
  • DOI: 10.1093/glycob/cwt054
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Trimeric Tn antigen on Syndecan-1 binds to integrins and enhances cancer metastasis via dynamic changes of membrane microdomains. (2013)
  • Author(s): Matsumoto Y, Zhang Q, Akita K, Nakada H, Hamamura K, Tsuchida A, Okajima T, Furukawa K, Urano T, Furukawa K
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 33 Pages: 24264-24276
  • DOI: 10.1074/jbc.m113.455006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 糖脂質糖鎖によるシグナルの制御のメカニズム (2015)
  • Author(s): 古川鋼一、大川祐樹、大海雄介、橋本登、古川圭子
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド（神戸市）
  • Year and Date: 2015-12-04
  • Invited
• [Presentation] ヒトmelanoma細胞におけるNeogenin細胞内ドメイン（NelCD）標的遺伝子の同定 (2015)
  • Author(s): 金子 慶、大川祐樹、橋本 登、大海雄介、山内祥生、岡島徹也、小谷典弘、本家孝一、古川圭子、古川鋼一
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 癌関連連鎖との協同作用により癌形質を発現する分子群の同定と作用機構 (2015)
  • Author(s): 古川鋼一,大川祐樹、橋本登、金子慶、小谷典弘、本家孝一、大海雄介、古川圭子
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-10-08
  • Int'l Joint Research / Invited
• [Presentation] GD3発現メラノーマにおけるNeogeninの悪性形質創出メカニズム (2014)
  • Author(s): 金子 慶、大川 祐樹、橋本 登、大海 雄介、小川 光貴、山内 祥生、小谷 典弘、本家 孝一、古川 圭子、古川 鋼一
  • Organizer: 第87回日本生化学会大会（2014年10月 京都）
  • Place of Presentation: 京都国際会議場、京都府京都市
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Interaction between Siglec-9 and sialylcarbohydrates enhances cancer phenotypes. (2014)
  • Author(s): Koichi Furukawa
  • Organizer: SialoGlyco2014
  • Place of Presentation: Gold Coast, Australia
  • Year and Date: 2014-09-07 – 2014-09-10
  • Invited
• [Presentation] スフィンゴ糖脂質機能の統合的理解 (2014)
  • Author(s): 古川鋼一、橋本 登、大川祐樹、大海雄介、金子 慶、古川圭子
  • Organizer: 第33回日本糖質学会年会
  • Place of Presentation: 名古屋大学豊田講堂、愛知県名古屋市
  • Year and Date: 2014-08-10 – 2014-08-12
  • Invited
• [Presentation] グリオーマモデルマウスにおけるガングリオシドの発現解析 (2014)
  • Author(s): 大川祐樹、百田洋之、加藤 彰、橋本 登、津田 裕介、大海雄介、古川圭子、夏目敦至、若林俊彦、古川鋼一
  • Organizer: 第33回日本糖質学会年会
  • Place of Presentation: 名古屋大学豊田講堂、愛知県名古屋市
  • Year and Date: 2014-08-10 – 2014-08-12
• [Presentation] Specificity and spatio-temporal dynamics of the interaction between glycosphingolipids and endogenous ligands. (2014)
  • Author(s): Koichi Furukawa, Yuji Kondo, Yasutomo Ito, Keiko Furukawa
  • Organizer: Glyco-T 2014, 9th International Symposium on Glycosyltransferases
  • Place of Presentation: Port, Portugal
  • Year and Date: 2014-06-18 – 2014-06-21
  • Invited
• [Presentation] Spatio-temporal dynamics of the interaction between glycosphingolipids and membrane molecules. (2014)
  • Author(s): Koichi Furukawa
  • Organizer: Gordon Research Conference, Glycolipid & and Sphingolipid Biology.
  • Place of Presentation: Ventura, CA, USA
  • Invited
• [Presentation] 複合糖質と糖鎖認識分子との相互作用の時空間的ダイナミクス、糖鎖フィールド：糖鎖がシグナル伝達を制御する原理 (2013)
  • Author(s): 古川鋼一、近藤裕史、松本康之、古川圭子
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Invited
• [Presentation] 糖鎖による悪性形質の制御機構、癌細胞の発症と進展に関わる糖鎖の作用機構 (2013)
  • Author(s): 古川鋼一、松本康之、橋本 登、大川祐樹、大海雄介、古川圭子
  • Organizer: 第３２回日本糖質学会
  • Place of Presentation: 大阪国際センター、大阪市
  • Invited
• [Book] Gangliosides Regulate Tumor Properties: With Focus on the Suppression of Metastasis-Associated ppGalNAc-T13 with GM1. In Sugar Chains Capter 4, Eds by T. Suzuki, Springer (2015)
  • Author(s): Frukawa K, Matsumoto Y, Zhang Q, Furukawa K
  • Total Pages: 288
  • Publisher: Springer
• [Book] Sugar Chains (2015)
  • Author(s): Furukawa K, Matsumoto Y, Zhang Q, Furukawa K
  • Total Pages: 288
  • Publisher: Springer
• [Book] Lipid Rafts (2014)
  • Author(s): Furukawa K, Ohmi Y, Ohkawa Y, Kondo Y, Ohkawa Y, Hashimoto N, Tajima O, Furukawa K
  • Total Pages: 268
  • Publisher: Nova Science Publishers
• [Book] Glycoscience: Biology and Medicine (2014)
  • Author(s): Koichi Furukawa, Yuhsuke Ohmi, Yuki Ohkawa, Noboru Hashimoto, Yoshio Yamauchi, Orie Tajima, Keiko Furukawa
  • Total Pages: 1568
  • Publisher: Springer
• [Book] Glycobiology of the Nervous System (2014)
  • Author(s): Koichi Furukawa, Yuhsuke Ohmi, Yuki Ohkawa, Orie Tajima, Keiko Furukawa
  • Total Pages: 584
  • Publisher: Springer
• [Book] α4-galactosyltransferase (A4GALT). In Handbook of Glycosyltransferases and Related Genes. (2014)
  • Author(s): Koichi Furukawa, Yuji Kondo, Keiko Furukawa
  • Publisher: Springer
• [Book] beta-1,4 N-acetylgalactosaminylH transferase 1,2 (B4GALNT1,2). In Handbook of Glycosyltransferases and Related Genes. (2014)
  • Author(s): Koichi Furukawa, Keiko Furukawa, Yuhsuke Ohmi, Yuki Ohkawa, Yoshio Yamauchi, Noboru Hashimoto, Orie Tajima
  • Publisher: Springer
• [Book] 神経疾患と糖鎖の関わり、Annual Revie神経2013 (2013)
  • Author(s): 古川鋼一、大海雄介、大川祐樹、古川圭子、田島織絵
  • Total Pages: 277
  • Publisher: （株）中外医学