N-glycosylated glycoproteome analysis of glycosyltransferase-modified mice for comprehensive understanding of glycan functions

• Project/Area Number: 24241073
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: NARIMATSU Hisashi 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, 招聘研究員 (40129581)
• 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) ; SATO Takashi 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, 主任研究員 (90371046) ; ANGATA Kiyohiko 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, 招聘研究員 (00611138) ; TOGAYACHI Akira 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, 主任研究員 (60392635) ; SUGAHARA Daisuke 産業技術総合研究所, 糖鎖医工学研究センター, 研究員 (00390766) ; TAKAHASHI Satoru 筑波大学, 医学医療系, 教授 (50271896) ; KUDO Takashi 筑波大学, 医学医療系, 准教授 (20288062)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥47,450,000 (Direct Cost: ¥36,500,000、Indirect Cost: ¥10,950,000); Fiscal Year 2014: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000); Fiscal Year 2013: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000); Fiscal Year 2012: ¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
• Keywords: 糖鎖 / 糖タンパク質 / 糖鎖機能 / グライコプロテオミクス / N－結合型糖鎖 / 遺伝子ノックアウトマウス / 糖転移酵素 / 糖ペプチド / グライコプロテオミクス解析 / IGOT法

Outline of Final Research Achievements

Identification of glycoproteins targeted by the glycosyltransferases is indispensable to understand the functions of glycans. This study aims large-scale identification of the glycoproteins specifically targeted by the glycosyltransferases using glycosyltransferase gene-deficient mice (knockout: KO mice). The comparative analyses of the glycan carrier molecules by a glycoproteomics technology (IGOT-LC/MS method) in wild type and KO mice identified a panel of the candidate carrier proteins. Understanding of the molecular characteristics and tendency commonly found in the target glycoproteins would accelerate the elucidation of the mechanism in selective glycosylation of specific glycan structures toward specific proteins.

Research Products

• [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] WURCS: the Web3 unique representation of carbohydrate structures. (2014)
  • Author(s): Tanaka K, Aoki-Kinoshita KF, Kotera M, Sawaki H, Tsuchiya S, Fujita N, Shikanai T, Kato M, Kawano S, Yamada I, Narimatsu H.
  • Journal Title: J Chem Inf Model. Volume: 54(6) Issue: 6 Pages: 1558-66
  • DOI: 10.1021/ci400571e
  • Peer Reviewed / Open Access
• [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] Differential glycan analysis of an endogenous glycoprotein: toward clinical implementation--from sample pretreatment to data standardization. (2014)
  • Author(s): Kuno A, Matsuda A, Unno S, Tan B, Hirabayashi J, Narimatsu H.
  • Journal Title: Methods Mol Biol. Volume: 1200 Pages: 265-85
  • DOI: 10.1007/978-1-4939-1292-6_23
  • ISBN: 9781493912919, 9781493912926
  • Peer Reviewed
• [Journal Article] Strategy for development of clinically useful glyco-biomarkers. (2014)
  • Author(s): Narimatsu H
  • Journal Title: Glycoconj J Volume: 6-7 Issue: 6-7 Pages: 403-7
  • DOI: 10.1007/s10719-014-9544-8
  • Peer Reviewed
• [Journal Article] Glycoproteomics approach for identifying Glycobiomarker candidate molecules for tissue type classification of non-small cell lung carcinoma. (2014)
  • Author(s): Hirao Y, Matsuzaki H, Iwaki J, Kuno A, Kaji H, Ohkura T, Togayachi A, Abe M, Nomura M, Noguchi M, Ikehara Y, Narimatsu H
  • Journal Title: J Proteome Res Volume: 13(11) Issue: 11 Pages: 4705-4716
  • DOI: 10.1021/pr5006668
  • Peer Reviewed
• [Journal Article] GlycoRDF: an ontology to standardize glycomics data in RDF. (2014)
  • Author(s): Ranzinger R, Aoki-Kinoshita KF, Campbell MP, Kawano S, Lutteke T, Okuda S, Shinmachi D, Shikanai T, Sawaki H, Toukach P, Matsubara M, Yamada I, Narimatsu H.
  • Journal Title: Bioinformatics Volume: 31(6) Issue: 6 Pages: 919-25
  • DOI: 10.1093/bioinformatics/btu732
  • Peer Reviewed
• [Journal Article] A heterozygous mutation of GALNTL5 affects male infertility with impairment of sperm motility (2014)
  • Author(s): Takasaki N, Tachibana K, Ogasawara S, Matsuzaki H, Hagiuda J, Ishikawa H, Mochida K, Inoue K, Ogonuki N, Ogura A, Noce T, Ito C, Toshimori K, Narimatsu H.
  • Journal Title: Proc Natl Acad Sci USA Volume: 111 Issue: 3 Pages: 1120-1125
  • DOI: 10.1073/pnas.1310777111
  • Peer Reviewed
• [Journal Article] Regulation of cell shape and adhesion by CD34. (2013)
  • Author(s): Ohnishi H, Sasaki H, Nakamura Y, Kato S, Ando K, Narimatsu H, Tachibana K.
  • Journal Title: Cell Adh Migr. Volume: 7 Issue: 5 Pages: 426-433
  • DOI: 10.4161/cam.25957
  • 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] Clgalt1-deficient mice exhibit thrombocytopenia due to abnormal terminal differentiation of megakaryocytes (2013)
  • Author(s): Kudo T, et al. (13人中8番目)
  • Journal Title: Blood Volume: 122 Issue: 9 Pages: 1649-1657
  • DOI: 10.1182/blood-2012-12-471102
  • Peer Reviewed
• [Journal Article] Stable isotope labeling of N-glycosylated peptides by enzymatic deglycosylation for mass spectrometry-based glycoproteomics (2013)
  • Author(s): 梶 裕之
  • Journal Title: Methods Mol Biol."Mass Spectrometry of Glycoprroteins" Volume: 951 Pages: 217-227
  • DOI: 10.1007/978-1-62703-146-2_14
  • ISBN: 9781627031455, 9781627031462
  • Peer Reviewed
• [Journal Article] Large-scale identification of target proteins of a glycosyltransferase isozyme by Lectin-IGOT-LC/MS, an LC/MS-based glycoproteomic approach (2012)
  • Author(s): Sugahara, D., Kaji, H., Sugihara, K., Asano, M., and Narimatsu, H.
  • Journal Title: Scientific Reports Volume: 2 Issue: 1 Pages: 680-680
  • DOI: 10.1038/srep00680
  • 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] 糖鎖解析による疾患バイオマーカー探索の最前線 (2014)
  • Author(s): 成松久
  • Organizer: 第146回日本医学会シンポジウム
  • Place of Presentation: 日本医師会館大講堂
  • Year and Date: 2014-12-18
  • Invited
• [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
  • Place of Presentation: Hyderabad,India
  • Year and Date: 2014-12-12
• [Presentation] From discovery of the first mammalian glycotransferase gene to the future task. (2014)
  • Author(s): Hisashi Narimatsu
  • Organizer: The 6th ACGG conference
  • Place of Presentation: Hyderabad,India.
  • Year and Date: 2014-12-10
  • Invited
• [Presentation] 糖鎖科学の進捗と疾患診断への応用 (2014)
  • Author(s): 成松久
  • Organizer: 第 66 回日本皮膚科学会西部支部学術大会
  • Place of Presentation: アルファあなぶきホール
  • Year and Date: 2014-11-28
  • Invited
• [Presentation] A heterozygous mutation of glycosyltransferase-like gene causes asthenozoospermia. (2014)
  • Author(s): Hisashi Narimatsu、Nobuyoshi Takasaki
  • Organizer: SFG & JSCR 2014 Joint Annual Meeting(Glycobiology)
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2014-11-19
  • Invited
• [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: 国立京都国際会館
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Combination of glycoproteomics technologies utilized in successful development of diagnostic systems. (2014)
  • Author(s): Hisashi Narimatsu
  • Organizer: HUPO 13th Annual World Congress
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2014-10-07
  • Invited
• [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 Annual World Congress
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2014-10-05 – 2014-10-08
• [Presentation] グライコプロテオミクス (2014)
  • Author(s): 成松久、梶 裕之、久野 敦
  • Organizer: 日本プロテオーム学会2014年会（JHUPO第12回大会）
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2014-07-18
  • Invited
• [Presentation] タンパク質特異的糖鎖修飾機構解明のための特定の糖鎖を持つ糖タンパク質の大規模同定 (2014)
  • Author(s): 佐藤隆、梶裕之、安形清彦、成松久
  • Organizer: 日本プロテオーム学会2014年会（JHUPO第12回大会）
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] 糖鎖付加位置選択的グライコーム解析技術の開発と応用 (2014)
  • Author(s): 梶裕之、富岡あづさ、鹿内俊秀、成松久
  • Organizer: 日本プロテオーム学会2014年会（JHUPO第12回大会）
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] コア3型糖鎖キャリアータンパク質の同定 (2014)
  • Author(s): 杜東寧、安形清彦、久野敦、富岡あづさ、藤田弥佳、梶裕之、成松久
  • Organizer: 日本プロテオーム学会2014年会（JHUPO第12回大会）
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2014-07-17 – 2014-07-18
• [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: 日本プロテオーム学会2014年会（JHUPO第12回大会）
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] 分析ターゲットとしての糖鎖の可能性 (2014)
  • Author(s): 成松久
  • Organizer: 第64回日本電気泳動学会シンポジウム
  • Place of Presentation: 文京学院大学本郷キャンパス
  • Year and Date: 2014-06-28
  • Invited
• [Presentation] Successful cases of translational research based on the glycoanalysis technologies. (2014)
  • Author(s): Hisashi Narimatsu
  • Organizer: GlycoT 2014
  • Place of Presentation: Port, Portugal
  • Year and Date: 2014-06-21
  • Invited
• [Presentation] 糖鎖科学に必要とされる基盤ツールの開発と、それを応用した糖鎖バイオマーカーの開発 (2014)
  • Author(s): 成松久
  • Organizer: シスメックスセミナー
  • Place of Presentation: 品川グランドコモンズ グランドホール
  • Year and Date: 2014-06-06
  • Invited
• [Presentation] Csgalnact1 is essential for normal chondrocyte layer formation. (2013)
  • Author(s): Takashi Sato, Takashi Kudo, Yuzuru Ikehara, Hirotaka Ogawa, Akira Togayachi, Masatsugu Ema, Satoru Takahashi, Koji Kimata, Hideto Watanabe 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
• [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
• [Presentation] Systematic identification of in vivo target proteins specific for a glycosyltransferases isozyme, β1,4-galactosyltransferase-I. (2013)
  • Author(s): Sugahara D, Kaji H, Sugihara K, Asano M, Narimatsu H
  • Organizer: 22nd International Symposium on Glycoconjugates (GLYCO22)
  • Place of Presentation: Dalian, China
• [Presentation] Large-scale identification of in vivo target proteins of glycosyltransferases by Lectin-IGOT-LC/MS, an LC/MS-based glycoproteomic approach using knock-out mouse. (2013)
  • Author(s): Hisashi Narimatsu
  • Organizer: 22nd International Symposium on Glycoconjugates (GLYCO22)
  • Place of Presentation: Dalian, China
  • Invited
• [Presentation] A glycosyltransferase-related gene, Galntl5, is a functional molecule indispensable to mature sperm formation. (2013)
  • Author(s): Hisashi Narimatsu
  • Organizer: International Symposium on Chemical Glycobiology
  • Place of Presentation: Shanghai, China
  • Invited
• [Presentation] ポリラクトサミン糖鎖が制御する細胞表層分子機能 (2013)
  • Author(s): 日本生化学会大会
  • Organizer: 日本生化学会大会
  • Place of Presentation: パシフィコ横浜、横浜
  • Invited
• [Presentation] An LC/MS-based glycoproteomic approach for systematic identification of in vivo target proteins specific for a glycosyltransferase isozyme, (2013)
  • Author(s): Sugahara D, Kaji H, Sugihara K, Asano M, Narimatsu H
  • Organizer: The 12th Human Proteome Organisation World Congress (12th HUPO)
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] Large-scale identification of glycoproteins having LDN glycans for mechanism elucidation in protein-specific glycosylation, (2013)
  • Author(s): Sato T, Kaji H, and Narimatsu H
  • Organizer: The 12th Human Proteome Organisation World Congress (12th HUPO)
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] C1galt1欠損マウスは巨核球の最終分化異常により血小板減少症を引き起こす (2013)
  • Author(s): 工藤崇、佐藤隆、萩原梢、上妻行則、山口高志、池原譲、濱田理人、松本健、依馬正次、村田聡一郎、大河内信弘、成松久、高橋智
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド、神戸
• [Presentation] The 3rd Pilot study on HGPI/HUPO
  • Author(s): 梶 裕之、成松 久
  • Organizer: 日本プロテオーム学会2012年大会
  • Place of Presentation: 東京都江東区青海 日本科学未来館
  • Invited
• [Presentation] Identification of target proteins specific for a glycosyltransferase isozyme by glycoproteomic analysis of a glyco-gene deleted model organism
  • Author(s): 菅原大介、成松 久
  • Organizer: International Symposium on Glyco-minded Biology of Diseases as a Basis of Pharmaceutical Sciences
  • Place of Presentation: 東京大学（文京区）
• [Presentation] Large-scale identification of target proteins of a glycosyltransferase isozyme by Lectin-IGOT-LC/MS, an LC/MS-based glycoproteomic approach
  • Author(s): 菅原大介、成松 久
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡市 福岡国際会議場
• [Presentation] A glycosyltransferase-related gene, Galntl5, has a role specific to functionally mature sperm formation in mammals
  • Author(s): 髙﨑延佳
  • Organizer: ACGG 2012 Conference, 4thAsian Communications of Glycobiology and Glycotechnology
  • Place of Presentation: Jeju Ialand (Korea)
  • Invited
• [Presentation] A toxic protein to cultured cells is functional only in mammalian mature sperm formation
  • Author(s): 髙﨑延佳、成松久
  • Organizer: Joint Meeting of The 45th annual Meeting of the Japanese Society of Developmental Biologists & The 64th Annual Meeting of the Japan Society for Cell Biology
  • Place of Presentation: 神戸市 神戸国際会議場
• [Book] 「医学のあゆみ」プロテオミクス、グライコミクス、そしてグライコプロテオミクスの時代へ (2014)
  • Author(s): 成松久
  • Publisher: 医歯薬出版「医学のあゆみ」
• [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
• [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): Takashi Sato and Hisashi Narimatsu
  • Total Pages: 1707
  • Publisher: Springer