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脳特異的な分岐型Oマンノース糖鎖がグリアアセンブリに果たす役割

Publicly Offered Research

Project AreaGlial assembly: a new regulatory machinery of brain function and disorders
Project/Area Number 26117522
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

北爪 しのぶ  国立研究開発法人理化学研究所, 疾患糖鎖研究チーム, 副チームリーダー (80301753)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
KeywordsOーマンノース糖鎖 / 脱髄 / 再ミエリン化 / 活性化アストロサイト / キュプリゾン / O-マンノース糖鎖 / アストロサイト / オリゴデンロサイト
Outline of Annual Research Achievements

私達は、脳特異的な分岐型O-マンノース糖鎖が、脱随時の再ミエリン化を制御していることを最近明らかにした(K. Kanekiyo, K. Inamori, S. Kitazume et al. J. Neurosci. 33, 10037-10047, 2013)。本研究では、脱随時に脳梁内で活性化されるアストロサイトが分岐型O-マンノース糖鎖の発現を増加させることに着目し、この糖鎖を検出するCat315抗体を用いて、脳梁内の活性化アストロサイトの解析を行った。脱随時に生じる活性化アストロサイトは通常大脳皮質内に見られる活性化アストロサイトのような星形の形状をしておらず、細がない形態であった。また、脱髄刺激してから2週間後に活性化アストロサイトが出現するが、cat315陽性アストロサイトの出現は遅く、6週後にやっと観察された。このCat315アストロサイトの起原を明らかにするため、現在Olig2-CreER:ROSA-GFP マウスにキュプリゾンを10週間投与し、タモキシフェン投与によって出現するGFP陽性細胞がCat315陽性となるかどうか解析中である。また、このCat315抗体は直鎖型O-Man糖鎖を認識してしまうという欠点を持っている。そのため、Gal-GlcNAc分岐O-Manペプチドとリコンビナント酵素を出発材料としてHNK-1エピトープを付加させたものを作製中であり、これを用いることで分岐型O-Man糖鎖に特異的な抗体を作製しようと考えている。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (11 results)

All 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Book (1 results)

  • [Int'l Joint Research] University of Saarland(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Glyco-redox, a link between oxidative stress and changes of glycans: Lessons from research on glutathione, reactive oxygen and nitrogen species to glycobiology.2016

    • Author(s)
      N. Taniguchi, Y. Kizuka, S. Takamatsu, E. Miyoshi, C. Gao, K. Suzuki, S. Kitazume, K. Ohtsubo
    • Journal Title

      Arch. Biochem. Biphys.

      Volume: 595 Pages: 72-80

    • DOI

      10.1016/j.abb.2015.11.024

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Visualizing Trimming Dependence of Biodistribution and Kinetics with Homo- and Heterogeneous N-Glycoclusters on Fluorescent Albumin2016

    • Author(s)
      A. Ogura, T. Tahara, S. Nozaki, K. Morimoto, Y. Kizuka, S. Kitazume, M. Hara, S. Kojima, H. Onoe, A. Kurbangalieva, N. Taniguchi, Y. Watanabe, K. Tanaka
    • Journal Title

      Sci. Rep.

      Volume: 6 Issue: 1 Pages: 21797-21797

    • DOI

      10.1038/srep21797

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Bisecting GlcNAc modification stabilizes BACE1 protein under oxidative stress conditions2016

    • Author(s)
      Kizuka Y, Nakano M, Kitazume S, Saito T, Saido TC, Taniguchi N
    • Journal Title

      Biochemical Journal

      Volume: 473 Issue: 1 Pages: 21-30

    • DOI

      10.1042/bj20150607

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer’s disease2015

    • Author(s)
      Yasuhiko Kizuka, Shinobu Kitazume, Reiko Fujinawa, Takashi Saito, Nobuhisa Iwata, Takaomi C. Saido, Miyako Nakano, Yoshiki Yamaguchi, Yasuhiro Hashimoto
    • Journal Title

      EMBO Mol. Med.

      Volume: 7(2) Issue: 2 Pages: 175-89

    • DOI

      10.15252/emmm.201404438

    • NAID

      120006799362

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clec4g (LSECtin) interacts with BACE1 and suppresses Aβ generation2015

    • Author(s)
      Kizuka Y, Kitazume S, Sato K, Taniguchi N
    • Journal Title

      FEBS Letters

      Volume: 589 Issue: 13 Pages: 1418-1422

    • DOI

      10.1016/j.febslet.2015.04.060

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell surface and in vivo interaction of dendrimeric N-glycoclusters.2015

    • Author(s)
      M. Taichi, S. Kitazume, K. Vong, R. Imamaki, A. Kurbangalieva, N. Taniguchi, and K. Tanaka
    • Journal Title

      Glycoconjugate J.

      Volume: 32 Issue: 7 Pages: 497-503

    • DOI

      10.1007/s10719-015-9594-6

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Polyamine modification by acrolein exclusively produces 1,5-diazacyclooctanes: a previously unrecognized mechanism for acrolein-mediated oxidative stress2014

    • Author(s)
      Tsutsui A, Imamaki R, Kitazume S, Hanashima S, Yamaguchi Y, Kaneda M, Oishi S, Fujii N, Kurbangalieva A, Taniguchi N, Tanaka K
    • Journal Title

      Org Biomol Chem.

      Volume: 12 Issue: 28 Pages: 5151-5157

    • DOI

      10.1039/c4ob00761a

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of platelet endothelial cell adhesion molecule (PECAM) with α2,6-sialylated glycan regulates its cell surface residency and anti-apoptotic role2014

    • Author(s)
      Kitazume, S., Imamaki, R., Kurimoto, A., Ogawa, K., Kato, M., Yamaguchi, Y., Tanaka, K., Ishida, H., Ando, H., Kiso, M., Hashii, N., Kawasaki, N. and Taniguchi, N.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 289 Issue: 40 Pages: 27604-27613

    • DOI

      10.1074/jbc.m114.563585

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Sweet role of platelet endothelial cell adhesion moleculr (PECAM) in understanding angiogenesis.2014

    • Author(s)
      S. Kitazume*, R. Imamaki, K. Ogawa, and N. Taniguchi
    • Journal Title

      Glycobiology

      Volume: 24 Issue: 12 Pages: 1260-1264

    • DOI

      10.1093/glycob/cwu094

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Book] Handbook of Glycosyltransferases and Related Genes. 2nd Edition.2014

    • Author(s)
      S. Kitazume
    • Publisher
      ST6Gal-I.
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-28  

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