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Understanding of glycosylation functions in activated lymphocytes

Research Project

Project/Area Number 21590063
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKyoto University

Principal Investigator

TAKEMATSU Hiromu  京都大学, 大学院・生命科学研究科, 准教授 (80324680)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsシアル酸 / 糖鎖 / レクチン / 認識 / リンパ球 / 胚中心 / T細胞 / 認識機構 / Bリンパ球 / ノックアウトマウス / 糖鎖認識 / カルシウム / 遺伝子相互作用
Research Abstract

In this grant, I explored functional aspects of N-glycolylneuraminic acid(Neu5Gc) in mouse lymphocytes to understand immunological function of sialic acid species modulation. Targeted disruption of CD22 and Neu5Gc-biosynthesis enzyme CMP-Neu5Ac hydroxylase(CMAH) resulted in the non-overlapping phenotypes in lymphocytes. Obtained data indicated that Neu5Gc, although that serves as high affinity glycan ligand for CD22, functions partly apart from CD22 ligand. This research results indicated that Neu5Gc has CD22-independent cellular autonomous function(s), that may not be limited in lymphocytes. Therefore, when mice were utilized as a model for human in biomedical research, it is strongly recommended to use cmah-null background to avoid confusion in the phenotypic analysis.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (47 results)

All 2012 2011 2010 2009

All Journal Article (24 results) (of which Peer Reviewed: 11 results) Presentation (12 results) Book (11 results)

  • [Journal Article] Tedder TFCD22 serves as a receptor for soluble IgM2012

    • Author(s)
      Adachi T, Harumiya S, Takematsu H, Kozutsumi Y, Wabl M, Fujimoto M
    • Journal Title

      Eur J Immunol

      Volume: 42(1) Pages: 241-247

    • Related Report
      2011 Final Research Report
  • [Journal Article] CD22 serves as a receptor for soluble IgM2012

    • Author(s)
      Adachi T, Harumiya S, Takematsu H, Kozutsumi Y, Wabl M, Fujimoto M, Tedder TF
    • Journal Title

      Eur J Immunol

      Volume: 42(1) Issue: 1 Pages: 241-247

    • DOI

      10.1002/eji.201141899

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kozutsumi Y Quantitative transcriptomic profiling of branching in a glycosphingolipid biosynthetic pathway2011

    • Author(s)
      Takematsu H, Yamamoto H, Naito-Matsui Y, Fujinawa R, Tanaka K, Okuno Y, Tanaka Y, Kyogashima M, Kannagi R
    • Journal Title

      J Biol Chem

      Volume: 286(31) Pages: 27214-27224

    • Related Report
      2011 Final Research Report
  • [Journal Article] CD22-Antagonists with nanomolar potency : The synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold2011

    • Author(s)
      Abdu-Allah HHM, Watanabe K, Completo GC, Sadagopan M, Hayashizaki K, Takaku C, Tamanaka T, Takematsu H, Kozutsumi Y, Paulson JC, Tsubata T, Ando H, Ishida H, Kiso M
    • Journal Title

      Bioorg and Med Chem

      Volume: 19(6) Pages: 1966-71

    • Related Report
      2011 Final Research Report
  • [Journal Article] Analysis of multiple compound-protein interactions reveals novel bioactive molecules2011

    • Author(s)
      Yabuuchi H, Niijima S, Takematsu H, Ida T, Hirokawa T, Hara T, Ogawa T, Minowa Y, Tsujimoto G, Okuno Y.
    • Journal Title

      Mol Syst Biol

      Volume: 7 Pages: 472-472

    • Related Report
      2011 Final Research Report
  • [Journal Article] Sphingosylphosphorylcholine and lysosulfatide have inverse regulatory function in monocytic cell differentiation into macrophages2011

    • Author(s)
      Yamamoto H, Naito Y, Okano M, Kanazawa T, Takematsu H, Kozutsumi Y
    • Journal Title

      Arch Biochem Biophys

      Volume: 506(1) Pages: 83-91

    • NAID

      120002770476

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Journal Article] Quantitative transcriptomic profiling of branching in a glycosphingolipid biosynthetic pathway2011

    • Author(s)
      Takematsu H, Yamamoto H, Naito-Matsui Y, Fujinawa R, Tanaka K, Okuno Y, Tanaka Y, Kyogashima M, Kannagi R, Kozutsumi Y
    • Journal Title

      J Biol Chem

      Volume: 286(31) Issue: 31 Pages: 27214-27224

    • DOI

      10.1074/jbc.m111.234526

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD22-antagonists with nanomolar potency : The synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold2011

    • Author(s)
      Abdu-Allah HHM, et al
    • Journal Title

      Bioorg and Med Chem

      Volume: 19(6) Pages: 1966-1971

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of multiple compound-protein interaction reveals novel bioactive molecules2011

    • Author(s)
      Yabuuchi H, et al
    • Journal Title

      Mol System Biol

      Volume: 7 Pages: 472-472

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of Ypk1 as a novel selective substrate for nitrogen starvation-triggered proteolysis requiring autophagy system and ESCRT machinery components2010

    • Author(s)
      Shimobayashi M, Takematsu H, Eiho K, Yamane Y, Kozutsumi Y
    • Journal Title

      J Biol Chem

      Volume: 285(47) Pages: 36984-94

    • Related Report
      2011 Final Research Report
  • [Journal Article] Synthesis and binding analysis of unique AG2 pentasaccharide to human Siglec-2 using NMR techniques2010

    • Author(s)
      Hanashima S, Sato KI, Naito Y, Takematsu H, Kozutsumi Y, Ito Y, Yamaguchi Y.
    • Journal Title

      Bioorg Med Chem

      Volume: 18(11) Pages: 3720-5

    • Related Report
      2011 Final Research Report
  • [Journal Article] Binding to gangliosides containing N-acetylneuraminic acid is sufficient to mediate the immunomodulatory properties of the non-toxic mucosal adjuvant LT-IIb(T13I)2010

    • Author(s)
      Takematsu H, Mandell L, Clare RL, Connell TD.
    • Journal Title

      Clin Vaccine Immunol

      Volume: 17(6) Pages: 969-78

    • Related Report
      2011 Final Research Report
  • [Journal Article] Immunological property of antibodies against N-glycolylneuraminic acid epitopes in cytidine monophospho-N-acetylneuraminic acid hydroxylase-deficient mice2010

    • Author(s)
      Tahara H, Ide K, Basnet NB, Tanaka Y, Matsuda H, Takematsu H, Kozutsumi Y, Ohdan H.
    • Journal Title

      J Immunol

      Volume: 184(6) Pages: 3269-75

    • Related Report
      2011 Final Research Report
  • [Journal Article] Identification of Ypk1 as a novel selective substrate for nitrogen starvation-triggered proteolysis requiring autophagy system and ESCRT machinery components2010

    • Author(s)
      Shimobayashi M, et al
    • Journal Title

      J Biol Chem

      Volume: 285(47) Pages: 36984-36994

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and binding analysis of unique AG2 pentasaccharide to human Siglec-2 using NMR techniques2010

    • Author(s)
      Hanashima S, et al
    • Journal Title

      Bioorg Med Chem

      Volume: 18(11) Pages: 3720-3725

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Binding to gangliosides containing N-acetylneuraminic acid is sufficient to mediate the immunomodulatory properties of the non-toxic mucosal adjuvant LT-IIb(T13I)2010

    • Author(s)
      Nawar HF, et al
    • Journal Title

      Clin Vaccine Immunol

      Volume: 17(6) Pages: 969-978

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunological property of antibodies against N-glycolylneuraminic acid epitopes in cytidine monophospho-N-acetylneuraminic acid hydroxylase-deficient mice2010

    • Author(s)
      Tahara H, et al
    • Journal Title

      J Immunol

      Volume: 184(6) Pages: 3269-3275

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunological property of antibodies against N-glycolylneuraminic acidepitopes in cytidine monophospho-N-acetylneuraminic acid hydroxylase-deficient mice2010

    • Author(s)
      Tahara H., et al.
    • Journal Title

      J Immunol VOL.184

      Pages: 3269-3275

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potent small molecule mouse CD22-inhibitors : exploring the interaction of the residue at C-2 of sialic acid scaffold2009

    • Author(s)
      Abdu-Allah HH, Watanabe K, Hayashizaki K, Takaku C, Tamanaka T, Takematsu H, Kozutsumi Y, Tsubata T, Ishida H, Kiso M.
    • Journal Title

      Bioorg Med Chem Lett

      Volume: 19(19) Pages: 5573-5

    • Related Report
      2011 Final Research Report
  • [Journal Article] Synthesis of biotinylated sialoside to probe CD22-ligand interactions2009

    • Author(s)
      Abdu-Allah HH, Watanabe K, Hayashizaki K, Iwayama Y, Takematsu H, Kozutsumi Y, Tsubata T, Ishida H, Kiso M.
    • Journal Title

      Terahedron Lett

      Volume: 50(31) Pages: 4488-4491

    • Related Report
      2011 Final Research Report
  • [Journal Article] B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase2009

    • Author(s)
      Cariappa A, Takematsu H, Liu H, Diaz S, Haider K, Boboila C, Kalloo G, Connole M, Shi HN, Varki N, Varki A, Pillai S.
    • Journal Title

      J Exp Med

      Volume: 206(1) Pages: 125-38

    • Related Report
      2011 Final Research Report
  • [Journal Article] Glycosphingolipids are not pivotal receptors for Subtilase cytotoxin in vivo : sensitivity analysis with glycosylation-defective mutant mice2009

    • Author(s)
      Kondo Y, Tokuda N, Fan X, Yamashita T, Honke K, Takematsu H, Togayachi A, Ohta M, Kozutsumi Y, Narimatsu H, Tajima O, Furukawa K, Furukawa K.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 378(2) Pages: 179-81

    • Related Report
      2011 Final Research Report
  • [Journal Article] Potent small molecule mouse CD22-inhibitors : exploring the interaction of the residue at C-2 of sialic acid scaffold.2009

    • Author(s)
      Abdu-Allah HH, et al
    • Journal Title

      Bioory Med Chem Lett. VOL.19

      Pages: 5573-5575

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of biotinylated sialoside to probe CD-22ligand interactions2009

    • Author(s)
      Abdu-Allah HH, et al
    • Journal Title

      Terahedron Lett VOL.50

      Pages: 4488-4491

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Cmah欠損マウスーシアル酸分子種ヒト化マウス2011

    • Author(s)
      竹松弘
    • Organizer
      第14回日本異種移植研究会
    • Place of Presentation
      広島大学広仁会館広島
    • Year and Date
      2011-12-10
    • Related Report
      2011 Final Research Report
  • [Presentation] Cmah欠損マウスーシアル酸分子種ヒト化マウス2011

    • Author(s)
      竹松弘
    • Organizer
      第14回日本異種移植研究会
    • Place of Presentation
      広島大学広仁会館(招待講演)
    • Year and Date
      2011-12-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] CIRES法を用いた活性化B細胞におけるスフィンゴ糖脂質の生合成分岐点での制御機構2011

    • Author(s)
      竹松弘
    • Organizer
      第6回スフィンゴテラピィ研究会
    • Place of Presentation
      米子観光センター米子
    • Year and Date
      2011-07-15
    • Related Report
      2011 Final Research Report
  • [Presentation] CIRES法を用いた活性化B細胞におけるスフィンゴ糖脂質の生合成分岐点での制御機構2011

    • Author(s)
      竹松弘
    • Organizer
      第6回スフィンゴテラピィ研究会
    • Place of Presentation
      米子観光センター(招待講演)
    • Year and Date
      2011-07-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Quantitative transcriptomic profiling of biosynthetic pathway of CD77, a marker for human germinal center B cells2011

    • Author(s)
      竹松弘
    • Organizer
      第449回難研セミナー.第21回難治疾患共同研究拠点セミナー
    • Place of Presentation
      東京医科歯科大学東京
    • Year and Date
      2011-01-17
    • Related Report
      2011 Final Research Report
  • [Presentation] Genetic understanding of biosynthetic pathway branching regulation by a novel phenotype-genotype correlation analysis, CIRES2010

    • Author(s)
      Takematsu H
    • Organizer
      2010 Annual Conference of the Society for Glycobiology
    • Place of Presentation
      St Pete Beach, USA
    • Year and Date
      2010-11-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Genetic understanding of glycosphingolipid biosynthetic pathway branching regulation by novel phenotype-genotype analysis, CIRES2010

    • Author(s)
      Takematsu H., Naito Y., Tanaka K., Kyogashima M., Kannagi R., Kozutsumi Y.
    • Organizer
      The 28th Naito conference on Glycan expression and regulation[I]
    • Place of Presentation
      Kanagawa
    • Year and Date
      2010-07-29
    • Related Report
      2011 Final Research Report
  • [Presentation] Genetic understanding of glycosphingolipid biosynthetic pathway branching regulation by novel phenotype-genotype analysis, CIRES2010

    • Author(s)
      Takematsu H
    • Organizer
      28^<th> Naito conference on glycan expression and regulation[I]
    • Place of Presentation
      Kanagawa, Japan
    • Year and Date
      2010-07-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] 新規表現型-遺伝型相関解析法を用いた糖鎖生合成分岐点の解析2010

    • Author(s)
      竹松弘
    • Organizer
      第12回生命科学研究科シンポジウム
    • Place of Presentation
      芝蘭会館稲森ホール京都
    • Year and Date
      2010-07-01
    • Related Report
      2011 Final Research Report
  • [Presentation] Genetic Understanding of Biosynthetic Pathway Branching Regulation by a Novel Phenotype-Genotype Correlation Analysis, CIRES2010

    • Author(s)
      Takematsu H., Naito Y., Yamamoto H., Okuno Y., Tanaka K., Kyogashima M., Kannagi R., Kozutsumi Y.
    • Organizer
      Annual conference of the society for glycobiology
    • Place of Presentation
      St Pete Beach
    • Related Report
      2011 Final Research Report
  • [Presentation] 生合成経路分岐点における制御機構のトランスクリプトームを用いた解析2009

    • Author(s)
      竹松弘, ら
    • Organizer
      第82回生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] 糖脂質CIRES(O/P)2009

    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド神戸
    • Related Report
      2011 Final Research Report
  • [Book] Yasunori Kozutsumic DNA microarray experiment : set up and execution2011

    • Author(s)
      Hiromu Takematsu, Reiko Fujinawa
    • Publisher
      Glycoscience Protocol online database
    • URL

      http://jcggdb.jp/GlycoPOD/protocolShow.action?nodeId=t118

    • Related Report
      2011 Final Research Report
  • [Book] スフィンゴ脂質が関わる免疫抑制とシグナル伝達化学と生物2011

    • Author(s)
      竹松弘, 小堤保則
    • Publisher
      日本農芸化学会
    • Related Report
      2011 Final Research Report
  • [Book] 非ヒト型シアル酸N-グリコリルノイラミン酸生化学事典2011

    • Author(s)
      竹松弘
    • Publisher
      朝倉書店
    • Related Report
      2011 Final Research Report
  • [Book] シアル酸分子種のヒト化マウス(Cmahノックアウトマウス)生体機能モデルと新しいリソース、リサーチツール2011

    • Author(s)
      竹松弘、内藤裕子、小堤保則
    • Publisher
      エル・アイ・シー
    • Related Report
      2011 Final Research Report
  • [Book] スフィンゴ脂質が関わる免疫抑制とシグナル伝達(化学と生物49(05))2011

    • Author(s)
      竹松弘, 小堤保則
    • Publisher
      日本農芸化学会
    • Related Report
      2011 Annual Research Report
  • [Book] 非ヒト形シアル酸N-グリコリルノイラミン酸(生化学事典, 田中啓二ら編)2011

    • Author(s)
      竹松弘
    • Publisher
      朝倉出版(印刷中)
    • Related Report
      2010 Annual Research Report
  • [Book] シアル酸分子種のヒト化マウス-Cmahノックアウトマウス(生体機能モデルと新しいリソース、リサーチツール、小幡裕一ら編)2011

    • Author(s)
      竹松弘
    • Publisher
      エル・アイ・シー
    • Related Report
      2010 Annual Research Report
  • [Book] Bリンパ球におけるシアル酸修飾機能解明に向けて生化学2010

    • Author(s)
      竹松弘
    • Publisher
      日本生化学会
    • Related Report
      2011 Final Research Report
  • [Book] Bリンパ球におけるシアル酸修飾機能解明に向けて(生化学 81(8))2010

    • Author(s)
      竹松弘
    • Publisher
      日本生化学会
    • Related Report
      2010 Annual Research Report
  • [Book] 相関解析法を組み込んだ新しいDNAマイクロアレイデータ解析法CIRES.糖鎖生合成系を例にとってタンパク質核酸酵素2009

    • Author(s)
      竹松弘、小堤保則
    • Publisher
      共立出版
    • Related Report
      2011 Final Research Report
  • [Book] B細胞抗原受容体シグナルのシアル酸脱アセチル化酵素による制御臨床免疫アレルギー科2009

    • Author(s)
      竹松弘
    • Publisher
      科学評論社
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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