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Recognition of sulfated hexosamine upon construction of the nervous system

Research Project

Project/Area Number 14082202
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionAichi Gakuin University (2004-2006)
Nagoya University (2002-2003)

Principal Investigator

MURAMATSU Takashi  Aichi Gakuin University, Faculty of Psychological and Physical Science, Professor (00030891)

Co-Investigator(Kenkyū-buntansha) MURAMATSU Hisako  Nagoya University, Graduate School of Medicine, Associate Professor (50182134)
Project Period (FY) 2002 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥88,200,000 (Direct Cost: ¥88,200,000)
Fiscal Year 2006: ¥18,000,000 (Direct Cost: ¥18,000,000)
Fiscal Year 2005: ¥18,000,000 (Direct Cost: ¥18,000,000)
Fiscal Year 2004: ¥18,000,000 (Direct Cost: ¥18,000,000)
Fiscal Year 2003: ¥18,000,000 (Direct Cost: ¥18,000,000)
Fiscal Year 2002: ¥16,200,000 (Direct Cost: ¥16,200,000)
KeywordsSulfotransferse / Proteoglycan / Neurogenesis / Auditory deficits / Brain injury / Keratan sulfate / Knockout mice / Midkine / ニューログリカンC / 神経前駆体細胞 / プレイオトロフィン / トランスジェニックマウス / スルホトランスフェラーゼ / ヘパラン硫酸 / N-アセチルグルコミン / 神経幹細胞 / IGnT / セレクチン / リンパ球ホーミング / パイエル板 / ポリ-N-アセチルラクトサミン / I抗原 / N-アセチルグルコサミン / N-アセチルガラクトサミン / 硫酸化 / コンドロイチン硫酸
Research Abstract

We generated mice deficient in N-acetylglucosamine 6-sulfotransferase-1 (GlcNAc6ST-1). These mice exhibited lower activity in lymphocyte homing to lymph nodes compared to wild-type mice, establishing that GlcNAc6ST-1 is involved in synthesis of L-selectin ligand. International collaboration yielded double knockout mice deficient in both GlcNAc6ST-1 and -2. Studies using the double knockout mice revealed that GlcNAc&ST-1 and -2 co-operate in production of L-selectin ligand. GlcNAc6ST-1 was also involved in synthesis of keratan sulfate. Glia scar formation upon brain injury was reduced in GlcNAc6ST-1 knockout mice, indicating that keratan sulfate hinders repair of injured brain through promotion of glia scar formation. Midkine is a heparin-binding growth factor, which promotes growth, survival and migration of target cells. Mice doubly deficient in both midkine and pleiotrophin, another member of the growth factor family, exhibited auditory deficits and female infertility, and was reduced in spontaneous locomotive activity. Using neural precursor cells derived from midkine-deficient mice, we found that midkine promotes growth and survival of neural precursor cells without affecting their differentiation capability. These activities are the basis of promotion of neurogenesis by midkine. The glycosaminoglycan structure required for strong binding to midkine was clarified to be repeated structures composed of chondroitin sulfate E units or heparan sulfate trisulfated units. As midkine receptors, proteoglycans, integrins and low density lipoprotein receptor-related proteins are important, and were proposed to form molecular complex in the presence of midkine. Upon process formation of oligodendrocyte precursor-like cells, neuroglycan C, a part time proteoglycan was also identified as a component of the receptor.

Report

(6 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (36 results)

All 2006 2005 2004 Other

All Journal Article (24 results) Publications (12 results)

  • [Journal Article] N-Acetylglucosamine 6-O-sulfotransferase-1 is required for brain keratan sulfate biosynthesis and glial scar formation after brain injury.2006

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

      Glycobiology 16

      Pages: 702-710

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Midkine, a heparin-binding growth factor, is expressed on neural precursor cells and promotes their growth.2006

    • Author(s)
      Zou, P, et al.
    • Journal Title

      J. Neurochem. 99

      Pages: 1470-1479

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors.2006

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

      Genes Cells 11

      Pages: 1405-1417

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Neuroglycan C is a novel midkine receptor involved in process elongation of oligodendroglial precursor-like cells.2006

    • Author(s)
      Ichihara-Tanaka, K, et al.
    • Journal Title

      J. Biol. Chem 281

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] N-acetylglucosamine 6-O-sulfotransferase-1 is required for brain keratan sulfate biosynthesis and glial scar formation after brain injury2006

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

      Glycobiology 16

      Pages: 702-710

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Midkine, a heparin-binding growth factor is expressed on neural precursor cells and promotes their growth2006

    • Author(s)
      Zou, P., et al.
    • Journal Title

      J. Neurochem. 99

      Pages: 1470-1479

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Female infertility in mice deficient in midkine and pleiotrophin, which form distinct family of growth factors2006

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

      Genes Cells 11

      Pages: 1405-1417

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Neuroglycan C is a novel midkine receptor involved in process elongenation of oligodendroglial precursor-like cells2006

    • Author(s)
      Ichihara-Tanaka, K., et al.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 30857-30864

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] N-Acetylglucosamine 6-O-sulfotransferase-1 is required for brain keratan sulfate biosynthesis and glial scar formation after brain injury.2006

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

      Glycobiology 16

      Pages: 702-710

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Midkine, a heparin-binding growth factor, is expressed on neural precursor cells and promotes their growth.2006

    • Author(s)
      Zou, P.et al.
    • Journal Title

      J.Neurochem. 99

      Pages: 1470-1479

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors.2006

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

      Genes Cells 11

      Pages: 1405-1417

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Neuroglycan C is a novel midkine receptor involved in process elongation of oligodendroglial precursor-like cells.2006

    • Author(s)
      Ichihara-Tanaka, K et al.
    • Journal Title

      J.Biol Chem. 281

      Pages: 30857-30864

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mice doubly deficient in the midkine and pleiotrophin genes exhibit deficits in the expression of beta-tectorin gene and in auditory response2006

    • Author(s)
      Zou, P.et al.
    • Journal Title

      Lab.Inv. 86

      Pages: 645-653

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Abnormalities caused by carbohydrate alterations in I β6-N-acetylglucosaminyltransferase-deficient mice.2005

    • Author(s)
      Chen, G. Y. ら
    • Journal Title

      Mol.Cell.Biol. 25

      Pages: 7828-7838

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Heparin-binding growth factor, pleiotrophin, mediates neuritogenic activity of embryonic pig brain-derived chondroitin sulfate/dermatan sulfate hybrid chains2005

    • Author(s)
      Bao, X. ら
    • Journal Title

      J.Biol.Chem 280

      Pages: 9180-9191

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mutational studies on endo-β-N-acetylglucosaminidase D which hydrolyzes core portion of asparagine-linked complex type oligosaccharides.2005

    • Author(s)
      Yamamoto, S. ら
    • Journal Title

      Glycoconj.J. 23

      Pages: 35-42

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venules.2005

    • Author(s)
      Uchimura, K. ら
    • Journal Title

      Nature Immunol. 8

      Pages: 1105-1113

    • Related Report
      2005 Annual Research Report
  • [Journal Article] α4β1- and α61-integrins are functional receptors for midkine, a heparin-binding growth factor.2004

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

      J. Cell Sci. 117

      Pages: 5405-5415

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] N-Acetylglucosamine 6-O-sulfotransferase-1 regulates expression of L-selectin ligands and lymphocyte homing.2004

    • Author(s)
      Uchimura, K, et al.
    • Journal Title

      J. Biol. Chem 279

      Pages: 35001-35008

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] α4β1- and α61-integrins are functional receptors for midkine, a heparin-binding growth factor2004

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

      J. Cell Sci 111

      Pages: 5405-5415

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] N-acetylglucosamine 6-O-sulfotransferase-1 regulates expression of L-selectin ligands and lymphocyte homing2004

    • Author(s)
      Uchimura, K., et al.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 35001-35008

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] α4β1- and α61-integrins are functional receptors for midkine, a heparin-binding growth factor2004

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

      J.Cell Sci. 117

      Pages: 5405-5415

    • Related Report
      2004 Annual Research Report
  • [Journal Article] N-acetylglucosamine 6-O-sulfotransferase-1 regulates expression of L-selectin ligands and lymphocyte homing.2004

    • Author(s)
      Uchimura, K. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 35001-35008

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Role of the carboxyl-terminal region in the activity of N-acetylglucosamine 6-O-sulfotransferase-1.2004

    • Author(s)
      Chen, L. et al.
    • Journal Title

      J.Biochem. 136

      Pages: 659-664

    • Related Report
      2004 Annual Research Report
  • [Publications] Sakaguchi, N.ら: "Receptor-type protein tyrosine phosphatase z as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons."Neurosci.Res.. 45. 219-224 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] El-Fasakhany, F.M.ら: "N-Acetylglucosamine-6-sulfotransferase-1 : production in the baculovirus system and its applications to the synthesis of a sulfated oligosaccharide and to the modification of oligosaccharides in fibrinogen."J.Biochem.. 133. 287-293 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Pilp, N.J.ら: "Loss of MCT1, MCT3, and MCT4 expression in the retinal pigment epithelium and neural retina of the 5A11/basigin-null mouse."Invest.Ophthalmol.Vis.Sci.. 44. 1305-1311 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ochrietor, J.D.ら: "Retina-specific expression of 5A11/Basigin-2, a member of the immunoglobulin gene superfamily."Invest.Ophthalmol.Vis.Sci.. 44. 4086-4096 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Muramatsu, T.ら: "Basigin (CD147) : a multifunctional transmembrane protein involved in reproduction, neural function, inflammation and tumor-invasion."Histol.Histopathol.. 18. 981-987 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Muramatsu, T.ら: "Recognition of glycosaminoglycans by midkine."Methods Enzymol.. 363. 365-376 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Peng Zou: "Glycosaminoglycan structures required for strong binding to midkine, a heparin binding growth factor"Glycobiology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Fathy M.El-Fasakhany: "N-Acetylglucosamine-6-sulfotransferase-1: production in thebaculovirus system and its applications to the synthesis of a sulfated oligosaccharide and to the modification of oligosaccharides in fibrinogen"Journal of Biochemistry. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kenji Uchimura: "Specificities of N-acetylglucosamine-6-O-sulfotransferases in relation to L-selectin ligand synthesis and tumor-associated enzyme expression"The Journal of Biological Chemistry. 277. 3979-3984 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akiko Kanamori: "Distinct sulfation requirements of selectins disclosed using cells that support rolling mediated by all three selectins under shear flow. L-selectin prefers carbohydrate 6-sulfation to tyrosine sulfation, whereas P-selectin does not"The Journal of Biological Chemistry. 277. 32578-32586 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nahoko Sakaguchi: "Receptor-type protein tyrosine phosphatase ζ as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons"Neuroscience Research. 45. 219-224 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takashi Muramatsu: "Midkine and pleiotrophin : two related proteins involved in development, survival, inflammation and tumorigenesis"Journal of Biochemistry. 132. 359-371 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2018-03-28  

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