Elucidation of regulation/control mechanisms in glycan-mediated functions of cell-surface biomolecules.

• Project/Area Number: 24770138
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: TOGAYACHI Akira 独立行政法人産業技術総合研究所, 糖鎖創薬技術研究センター, 主任研究員 (60392635)
• Co-Investigator(Renkei-kenkyūsha): KAJI Hiroyuki 産業技術総合研究所, 糖鎖創薬技術研究センター・標的糖鎖探索チーム, 研究チーム長 (80214302)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 糖鎖 / ポリラクトサミン / 糖転移酵素 / β1,3-N-アセチルグルコサミン転移酵素 / 糖タンパク質 / グライコプロテオミクス解析 / 免疫系 / β1,3- N-アセチルグルコサミン転移酵素 / 免疫 / ポリ-N-アセチルラクトサミン / N-アセチルグルコサミン転移酵素 / グライコプロテオミクス / 糖鎖機能

Outline of Final Research Achievements

Glycosyltransferase gene-deficient mice show various abnormalities in biological functions. To analyze the mechanism, it is important to identify the glycoproteins targeted by the glycosyltransferases (glycan carrier molecules). In this study, we focused on polylactosamine glycans and identified the carrier molecules of polylactosaminoglycans using glycoproteomics technology. Glycopeptides were captured with the lectins specifically bind to polylactosamine glycans. Comparative glycoproteome analysis of the captured glycopeptides identified the target glycoprotein candidates. Bioinformatics analysis of the obtained carrier molecules found common characteristics and tendency in the molecular nature.

Research Products

• [Journal Article] RNAi screening of human glycogene orthologs in the nematode Caenorhabditis elegans and the construction of the C. elegans glycogene database. (2014)
  • Author(s): Akiyoshi S, Nomura KH, Dejima K, Murata D, Matsuda A, Kanaki N, Takaki T, Mihara H, Nagaishi T, Furukawa S, Ando KG, Yoshina S, Mitani S, Togayachi A, Suzuki Y, Shikanai T, Narimatsu H, Nomura K.
  • Journal Title: Glycobiology Volume: 25(1) Issue: 1 Pages: 8-20
  • DOI: 10.1093/glycob/cwu080
  • Peer Reviewed / Open Access
• [Journal Article] Mice lacking α1,3-fucosyltransferase 9 exhibit modulation of in vivo immune responses against pathogens (2014)
  • Author(s): Kashiwazaki H, Kakizaki M, Ikehara Y, Togayachi A, Narimatsu H, Watanabe R
  • Journal Title: Pathol Int Volume: 64(5) Issue: 5 Pages: 199-208
  • DOI: 10.1111/pin.12159
  • Peer Reviewed
• [Journal Article] The Lewis X-related α1,3-Fucosyltransferase, Fut10, Is Required for the Maintenance of Stem Cell Populations. (2013)
  • Author(s): Kumar A, Torii T, Ishino Y, Muraoka D, Yoshimura T, Togayachi A, Narimatsu H, Ikenaka K, Hitoshi S.
  • Journal Title: J Biol Chem. Volume: 288 Issue: 40 Pages: 28859-28868
  • DOI: 10.1074/jbc.m113.469403
  • Peer Reviewed
• [Journal Article] Functional Analysis of &beta;1,3-<I>N</I>-Acetylglucosaminyltransferases and Regulation of Immunological Function by Polylactosamine (2012)
  • Author(s): 栂谷内晶、成松久
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 24 Issue: 137 Pages: 95-111
  • DOI: 10.4052/tigg.24.95
  • NAID: 10030975922
  • ISSN: 0915-7352, 1883-2113
  • Peer Reviewed
• [Presentation] Comprehensive identification of glycoproteins carrying Lewis x and site-specific glycan alteration in Fut9 knockout mice. (2014)
  • Author(s): Erika Noro, Akira Togayachi, Takashi Sato, Azusa Tomioka, Mika Fujita, Masako Sukegawa, Nami Suzuki, Hiroyuki Kaji, Hisashi Narimatsu.
  • Organizer: The 6th ACGG conference, Hyderabad
  • Place of Presentation: India
  • Year and Date: 2014-12-12
• [Presentation] α1,3-フコース転移酵素９ノックアウトマウスを用いた糖鎖および糖タンパク質の網羅的な解析 (2014)
  • Author(s): 野呂絵里花、栂谷内晶、佐藤隆、富岡あづさ、藤田弥佳、助川昌子、鈴木奈美、梶裕之、成松久
  • Organizer: 第８７回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Comprehensive identification of glycoproteins carrying Lewis x and site-specific glycan alteration in Fut9 knockout mice. (2014)
  • Author(s): Erika Noro, Akira Togayachi, Takashi Sato, Azusa Tomioka, Mika Fujita, Masako Sukegawa, Nami Suzuki, Hiroyuki Kaji, Hisashi Narimatsu
  • Organizer: HUPO 13th World Congress
  • Place of Presentation: Madrid (Spain)
  • Year and Date: 2014-10-05 – 2014-10-08
• [Presentation] α1,3-フコース転移酵素９ノックアウトマウスを用いた糖鎖および糖タンパク質の網羅的な解析 (2014)
  • Author(s): 野呂絵里花、栂谷内晶、佐藤隆、富岡あづさ、藤田弥佳、助川昌子、鈴木奈美、梶裕之、成松久
  • Organizer: 日本ヒトプロテオーム学会(JHUPO) 第12回大会
  • Place of Presentation: 筑波
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] ポリラクトサミン糖鎖が制御する細胞表層分子機能（Function of cell surface molecules regulated by polylactosamine chains.） (2013)
  • Author(s): 栂谷内 晶
  • Organizer: 日本生化学会大会
  • Place of Presentation: パシフィコ横浜、横浜
  • Invited
• [Presentation] Biological function of polylactosamine chains on cell surface in immune system. (2013)
  • Author(s): Akira Togayachi, Takashi Sato, Yuzuru Ikehara, and Hisashi Narimatsu
  • Organizer: 日本組織培養学会（JTCA 2013）
  • Place of Presentation: 産総研共用講堂、つくば
• [Book] "Polylactosamine and immunity.", Glycoscience: Biology and Medicine.（分担執筆） (2015)
  • Author(s): Akira Togayachi
  • Total Pages: 1568
  • Publisher: Springer
• [Book] Handbook of Glycosyltransferases and Related Genes. 2nd edition. (分担執筆) (2013)
  • Author(s): Akira Togayachi and Hisashi Narimatsu
  • Total Pages: 1707
  • Publisher: Springer
• [Book] Handbook of Glycosyltransferases and Related Genes. 2nd edition. (分担執筆) (2013)
  • Author(s): Kiyohiko Angata, Takashi Sato, Akira Togayachi and Hisashi Narimatsu
  • Total Pages: 1707
  • Publisher: Springer