Updated on 2022/07/05

写真a

 
OKAJIMA, Tetsuya
 
Organization
Institute for Glyco-core Research Professor
Graduate School of Medicine Professor
Graduate School
Graduate School of Medicine
Title
Professor
Contact information
メールアドレス

Degree 1

  1. 博士(医学) ( 2000.3   名古屋大学 ) 

Research Interests 1

  1. Protein domain-specific glycans

Research Areas 1

  1. Others / Others  / Biochemistry

Current Research Project and SDGs 2

  1. 新型糖鎖による生体機能制御機構

  2. 糖鎖によるNotchシグナルの制御

Research History 10

  1. Nagoya University   Professor

    2021.1

  2. Nagoya University   Institute of Liberal Arts and Sciences

    2018.4

  3. Nagoya University   Institute for Advanced Research

    2016.10

  4. 名古屋大学大学院   医学系研究科   教授

    2015.11

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    Country:Japan

  5. Nagoya University   Graduate School of Medicine Program in Integrated Medicine Biological Chemistry   Professor

    2015.11

  6. 名古屋大学大学院医学系研究科准教授

    2009.10

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    Country:Japan

  7. 名古屋大学大学院医学系研究科講師

    2008.4 - 2009.9

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    Country:Japan

  8. 名古屋大学大学院生命農学研究科応用生命化学講座(分子生体制御学) 助教

    2007.4 - 2008.3

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    Country:Japan

  9. 名古屋大学大学院生命農学研究科応用生命化学講座(分子生体制御学)助手

    2005.12 - 2007.3

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    Country:Japan

  10. 名古屋大学医学部非常勤講師

    2005.6 - 2005.12

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    Country:Japan

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Education 2

  1. Nagoya University

    1996.4 - 2000.2

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    Country: Japan

  2. Nagoya University   Faculty of Medicine

    1990.4 - 1996.3

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    Country: Japan

Professional Memberships 3

  1. 日本生化学会

  2. 日本糖質学会

  3. 日本分子生物学会

Awards 4

  1. 日本糖質学会奨励賞

    2009  

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    Country:Japan

  2. Career Development Award

    2006   Human Frontier Science Program  

  3. JB/OUPポスター賞

    2009   日本生化学会/オックスフォード大学出版局  

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    「細胞外O-GlcNAc修飾機構の生化学的解析」

  4. 日本生化学会奨励賞

    2010  

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    Country:Japan

 

Papers 92

  1. Glycoproteomics of NOTCH1 EGF repeat fragments overexpressed with different glycosyltransferases in HEK293T cells reveals insights into O-GlcNAcylation of NOTCH1

    Tsukamoto Yohei, Ogawa Mitsutaka, Yogi Kentarou, Tashima Yuko, Takeuchi Hideyuki, Okajima Tetsuya

    GLYCOBIOLOGY     2022.3

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  2. Significant Roles of Notch O-Glycosylation in Cancer

    Wang Weiwei, Okajima Tetsuya, Takeuchi Hideyuki

    MOLECULES   Vol. 27 ( 6 )   2022.3

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  3. Ganglioside GD2 enhances malignant properties of melanoma by co-operating with integrin.

    Farhana Yesmin, Bhuiyan Robiul H., Ohmi Yuhsuke, Horiuchi Momoka, Okajima Tetsuya, Yamamoto Satoko, Furukawa Keiko, Furukawa Koichi

    CANCER SCIENCE   Vol. 113   page: 1104 - 1104   2022.2

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    Language:Japanese  

    Web of Science

  4. Unique effects of expression of asialo-series ganglioside GD1alpha in human cancer cell lines

    Robiul Bhuiyan, Yesmin Farhana, Kondo Yuji, Ohkawa Yuki, Ohmi Yuhsuke, Zhang Pu, Okajima Tetsuya, Furukawa Keiko, Furukawa Koichi

    CANCER SCIENCE   Vol. 113   page: 379 - 379   2022.2

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    Language:Japanese  

    Web of Science

  5. Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins

    Yesmin Farhana, Bhuiyan Robiul H., Ohmi Yuhsuke, Yamamoto Satoko, Kaneko Kei, Ohkawa Yuki, Zhang Pu, Hamamura Kazunori, Cheung Nai-Kong V., Kotani Norihiro, Honke Koichi, Okajima Tetsuya, Kambe Mariko, Tajima Orie, Furukawa Keiko, Furukawa Koichi

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 23 ( 1 )   2022.1

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  6. Eogt-catalyzed O-GlcNAcylation

    Lo Pei-Wen, Okajima Tetsuya

    TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY   Vol. 34 ( 197 ) page: E1 - E6   2022.1

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    Language:Japanese  

    DOI: 10.4052/tigg.2033.1E

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  7. Other Classes of Eukaryotic Glycans

    Haltiwanger RS, Wells L, Freeze HH, Jafar-Nejad H, Okajima T, Stanley P, Varki A, Cummings RD, Esko JD, Stanley P, Hart GW, Aebi M, Mohnen D, Kinoshita T, Packer NH, Prestegard JH, Schnaar RL, Seeberger PH

        2022

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    DOI: 10.1101/glycobiology.4e.13

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  8. St8sia1-deficiency in mice alters tumor environments of gliomas, leading to reduced disease severity Reviewed

    Thane Pu, Ohkawa Yuki, Yamamoto Satoko, Momota Hiroyuki, Kato Akira, Kaneko Kei, Natsume Atsushi, Farhana Yesmin, Ohmi Yuhsuke, Okajima Tetsuya, Bhuiyan Robiul H., Wakabayashi Toshihiko, Furukawa Keiko, Furukawa Koichi

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 83 ( 3 ) page: 535 - 549   2021.8

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  9. Majority of alpha2,6-sialylated glycans in the adult mouse brain exist in O-glycans: SALSA-MS analysis for knockout mice of alpha2,6-sialyltransferase genes Reviewed

    Ohmi Yuhsuke, Nishikaze Takashi, Kitaura Yoko, Ito Takako, Yamamoto Satoko, Sugiyama Fumihiro, Matsuyama Makoto, Takahashi Yoshimasa, Takeda Akira, Kawahara Toshio, Okajima Tetsuya, Furukawa Keiko, Furukawa Koichi

    GLYCOBIOLOGY   Vol. 31 ( 5 ) page: 557 - 570   2021.5

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  10. Bioinformatics and Functional Analyses Implicate Potential Roles for EOGT and L-fringe in Pancreatic Cancers Reviewed

    Barua Rashu, Mizuno Kazuyuki, Tashima Yuko, Ogawa Mitsutaka, Takeuchi Hideyuki, Taguchi Ayumu, Okajima Tetsuya

    MOLECULES   Vol. 26 ( 4 )   2021.2

  11. Current Views on the Roles of O-Glycosylation in Controlling Notch-Ligand Interactions Reviewed

    Saiki Wataru, Ma Chenyu, Okajima Tetsuya, Takeuchi Hideyuki

    BIOMOLECULES   Vol. 11 ( 2 )   2021.2

  12. Roles of asialo-series ganglioside GD1 alpha in human cancer cell lines. Reviewed

    Bhuiyan Robiul H., Yesmin Farhana, Kondo Yuji, Ohkawa Yuki, Ohmi Yuhsuke, Zhang Pu, Okajima Tetsuya, Furukawa Keiko, Furukawa Koichi

    CANCER SCIENCE   Vol. 112   page: 679 - 679   2021.2

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    Language:Japanese  

    Web of Science

  13. Ganglioside GD2 enhances malignant properties of melanoma by co-operating with integrin. Reviewed

    Yesmin Farhana, Bhuiyan Robiul H., Ohmi Yuhsuke, Okajima Tetsuya, Yamamoto Satoko, Furukawa Keiko, Furukawa Koichi

    CANCER SCIENCE   Vol. 112   page: 699 - 699   2021.2

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    Language:Japanese  

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  14. N-glycans on EGF domain-specific O-GlcNAc transferase (EOGT) facilitate EOGT maturation and peripheral endoplasmic reticulum localization

    Alam Sayad Md Didarul, Tsukamoto Yohei, Ogawa Mitsutaka, Senoo Yuya, Ikeda Kazutaka, Tashima Yuko, Takeuchi Hideyuki, Okajima Tetsuya

    GLYCOBIOLOGY   Vol. 30 ( 12 ) page: 1031 - 1032   2020.12

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  15. Comprehensive O-GlcNAc glycoproteomics on NOTCH1 EGF repeats refined the sequons for O-GlcNAcylation and uncovered unique Lewis X epitopes in mammals

    Ogawa Mitsutaka, Tsukamoto Yohei, Yogi Kenntarou, Senoo Yuya, Ikeda Kazutaka, Takeuchi Hideyuki, Okajima Tetsuya

    GLYCOBIOLOGY   Vol. 30 ( 12 ) page: 1086 - 1087   2020.12

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  16. 3 '-Sialyllactose on Notch: NOTCH1 functions as a scafold of O-linked, 3 '-sialyllactosylated glycans

    Tsukamoto Yohei, Aoki Kazuhiro, Narimatsu Yoshiki, Urata Yusuke, Saiki Wataru, Ogawa Mitsutaka, Clausen Henrik, Tiemeyer Michael, Okajima Tetsuya, Takeuchi Hideyuki

    GLYCOBIOLOGY   Vol. 30 ( 12 ) page: 1119 - 1120   2020.12

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  17. Glycoproteomic analysis identifies cryptdin-related sequence 1 as O-glycosylated protein modified with alpha 1,2-fucose in the small intestine Reviewed

    Hashiguchi Hiroki, Tsukamoto Yohei, Ogawa Mitsutaka, Tashima Yuko, Takeuchi Hideyuki, Nakamura Masanao, Kawashima Hiroki, Fujishiro Mitsuhiro, Okajima Tetsuya

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   Vol. 695   page: 108653   2020.11

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    DOI: 10.1016/j.abb.2020.108653

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  18. Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs Reviewed

    Ma Chenyu, Takeuchi Hideyuki, Hao Huilin, Yonekawa Chizuko, Nakajima Kazuki, Nagae Masamichi, Okajima Tetsuya, Haltiwanger Robert S., Kizuka Yasuhiko

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 21 ( 17 )   2020.9

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    DOI: 10.3390/ijms21176007

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  19. Aminoglycosides are efficient reagents to induce readthrough of premature termination codon in mutant B4GALNT1 genes found in families of hereditary spastic paraplegia.

    Yesmin F, Bhuiyan RH, Ohmi Y, Ohkawa Y, Tajima O, Okajima T, Furukawa K, Furukawa K

    Journal of biochemistry   Vol. 168 ( 2 ) page: 103 - 112   2020.8

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    DOI: 10.1093/jb/mvaa041

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  20. N-Glycans on EGF domain-specificO-GlcNAc transferase (EOGT) facilitate EOGT maturation and peripheral endoplasmic reticulum localization

    Alam Sayad Md. Didarul, Tsukamoto Yohei, Ogawa Mitsutaka, Senoo Yuya, Ikeda Kazutaka, Tashima Yuko, Takeuchi Hideyuki, Okajima Tetsuya

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 295 ( 25 ) page: 8560 - 8574   2020.6

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    DOI: 10.1074/jbc.RA119.012280

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  21. Contribution of extracellular O-GlcNAc to the stability of folded epidermal growth factor-like domains and Notch1 trafficking

    Ogawa Mitsutaka, Tashima Yuko, Sakaguchi Yamato, Takeuchi Hideyuki, Okajima Tetsuya

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 526 ( 1 ) page: 184 - 190   2020.5

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    DOI: 10.1016/j.bbrc.2020.03.066

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  22. Xylosyl Extension of O-Glucose Glycans on the Extracellular Domain of NOTCH1 and NOTCH2 Regulates Notch Cell Surface Trafficking

    Urata Yusuke, Saiki Wataru, Tsukamoto Yohei, Sago Hiroaki, Hibi Hideharu, Okajima Tetsuya, Takeuchi Hideyuki

    CELLS   Vol. 9 ( 5 )   2020.5

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    DOI: 10.3390/cells9051220

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  23. The ceramide moiety of disialoganglioside (GD3) is essential for GD3 recognition by the sialic acid-binding lectin SIGLEC7 on the cell surface

    Hashimoto Noboru, Ito Shizuka, Tsuchida Akiko, Bhuiyan Robiul H., Okajima Tetsuya, Yamamoto Akihito, Furukawa Keiko, Ohmi Yuhsuke, Furukawa Koichi

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 294 ( 28 ) page: 10833 - 10845   2019.7

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    DOI: 10.1074/jbc.RA118.007083

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  24. Extracellular O-GlcNAc: From Discovery to Current Developments

    Okajima Tetsuya

    TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY   Vol. 31 ( 181 ) page: SE57 - SE58   2019.7

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    DOI: 10.4052/tigg.1927.2SE

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  25. Structure and function of extracellular O-GlcNAc

    Ogawa Mitsutaka, Okajima Tetsuya

    CURRENT OPINION IN STRUCTURAL BIOLOGY   Vol. 56   page: 72 - 77   2019.6

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  26. Loss of Enzyme Activity in Mutated B4GALNT1 Gene Products in Patients with Hereditary Spastic Paraplegia Results in Relatively Mild Neurological Disorders: Similarity with Phenotypes of B4galnt1 Knockout Mice

    Bhuiyan Robiul H., Ohmi Yuhsuke, Ohkawa Yuki, Zhang Pu, Takano Maiko, Hashimoto Noboru, Okajima Tetsuya, Furukawa Keiko, Furukawa Koichi

    NEUROSCIENCE   Vol. 397   page: 94-106   2019.1

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    DOI: 10.1016/j.neuroscience.2018.11.034

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  27. Structure and function of extracellular O-GlcNAc Invited Reviewed

    Mitsutaka Ogawa, Tetsuya Okajima

    Current Opinion in Structural Biology   Vol. 56   page: 72-77   2019

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  28. Whole mount staining of retina

    Mitsutaka Ogawa, Tetsuya Okajima

    bio-101   Vol. 8 ( 19 ) page: e3034   2018.10

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    DOI: 10.21769/BioProtoc.3034

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  29. Isolation of Murine Brain and Lung Microvascular Endothelial Cells Invited Reviewed

    Ailing Zhang, Shogo Sawaguchi, Entzu Wan, Mitsutaka Ogawa, Tetsuya Okajima

    bio-101     2018.8

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    DOI: 10.21769/BioProtoc.2984

  30. Congenital diseases caused by defective O-glycosylation of Notch receptors

    Tashima Yuko, Okajima Tetsuya

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 80 ( 3 ) page: 299-307   2018.8

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    DOI: 10.18999/nagjms.80.3.299

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  31. Structural Divergence in <i>O</i>-GlcNAc Glycans Displayed on Epidermal Growth Factor-like Repeats of Mammalian Notch1.

    Ogawa M, Senoo Y, Ikeda K, Takeuchi H, Okajima T

    Molecules (Basel, Switzerland)   Vol. 23 ( 7 )   2018.7

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    DOI: 10.3390/molecules23071745

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  32. NOTCH SIGNALING A sweet strategy

    Okajima Tetsuya

    NATURE CHEMICAL BIOLOGY   Vol. 14 ( 1 ) page: 3-4   2018.1

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    DOI: 10.1038/nchembio.2532

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  33. Protocol for Notch-ligand Binding Assays Using Dynabeads Invited Reviewed

    bio-protocol     2017.10

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    DOI: 10.21769/BioProtoc.2582

  34. O-GlcNAc on NOTCH1 EGF repeats regulates ligand-induced Notch signaling and vascular development in mammals

    Sawaguchi Shogo, Varshney Shweta, Ogawa Mitsutaka, Sakaidani Yuta, Yagi Hirokazu, Takeshita Kyosuke, Murohara Toyoaki, Kato Koichi, Sundaram Subha, Stanley Pamela, Okajima Tetsuya

    ELIFE   Vol. 6   2017.4

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    DOI: 10.7554/eLife.24419

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  35. Neogenin defined as a GD3-associated molecule by enzyme-mediated activation of radical sources confers malignant properties via intra-cytoplasmic domain in melanoma cells.  Reviewed

    Kaneko K, Ohkawa Y, Hashimoto N, Ohmi Y, Kotani N, Honke K, Ogawa M, Okajima T, Furukawa K, Furukawa K

    J. Biol. Chem.   Vol. 291   page: 16630-16643   2016

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  36. Impaired O-linked N-acetylglucosaminylation in the endoplasmic reticulum by mutated EGF domain-specific O-linked N-acetylglucosamine transferase found in Adams-Oliver syndrome.

    Ogawa M, Sawaguchi S, Kawai T, Nadano D, Matsuda T, Yagi H, Kato K, Furukawa K, Okajima T.

    J Biol Chem     page: in press   2015

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  37. O-fucose monosaccharide of Drosophila Notch has a temperature-sensitive function and cooperates with O-glucose glycan in Notch transport and Notch signaling activation. Reviewed

    Ishio A, Sasamura T, Ayukawa T, Kuroda J, Ishikawa HO, Aoyama N, Matsumoto K, Gushiken T, Okajima T, Yamakawa T, Matsuno K.

    J Biol Chem     page: in press   2015

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  38. Extracellular O-linked beta-N-acetylglucosamine: Its biology and relationship to human disease. Invited Reviewed

    Ogawa M, Furukawa K, Okajima T.

    World J Biol Chem   Vol. 5   page: 224-230   2014

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  39. Trimeric Tn Antigen on Syndecan 1 Produced by ppGalNAc-T13 Enhances Cancer Metastasis via a Complex Formation with Integrin alpha5beta1 and Matrix Metalloproteinase 9. Reviewed

      Vol. 288   page: 24264-24276   2013

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  40. Post-weaning increases in the milk-fat globule EGF-factor VIII on fat globules in mouse milk and in the uptake of the fat globules by HC11 mammary epithelial cells. Reviewed

      Vol. 153   page: 31-41   2013

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  41. Allergenic potential of rice-pollen proteins: expression, immuno-cross reactivity and IgE-binding.

      Vol. 154   page: 195-205   2013

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  42. Dephosphorylation reduces passage of ovalbumin antigen through intestinal epithelial Caco-2 cell monolayers.

      Vol. 153   page: 347-354   2013

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  43. GTDC2 modifies O-mannosylated α-dystroglycan in the endoplasmic reticulum to generate N-acetyl-glucosamine epitopes reactive with CTD110.6 antibody. Reviewed

      Vol. 440   page: 88-93   2013

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  44. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1.

      Vol. 419   page: 14-19   2012

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  45. pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen. Reviewed

      Vol. 419   page: 7-13   2012

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  46. Discharge of solubilized and Dectin-1-reactive beta-glucan from macrophage cells phagocytizing insoluble beta-glucan particles: Involvement of reactive oxygen species (ROS)-driven degradation. Reviewed

      Vol. 421   page: 329-334   2012

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  47. O-linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell-matrix interactions Reviewed

      Vol. 2   page: 583   2011.12

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    DOI: 10.1038

  48. Specific O-glycosylation modifying epidermal growth factor domains.

      Vol. 83   page: 813-821   2011

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  49. Strong antibody reaction against glycosphingolipids injected in liposome-embedded forms in beta3GN-T5 knockout mice.

      Vol. 73   page: 137-146   2011

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  50. Secretion of three enzymes for fatty acid synthesis into mouse milk in association with fat globules, and rapid decrease of the secreted enzymes by treatment with rapamycin

      Vol. 508   page: 87-92   2011

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  51. Establishment of a Mammary Stromal Fibroblastic Cell Line for In Vitro Studies in Mice of Mammary Adipocyte Differentiation. Reviewed

    Nakatani H, Aoki N, Okajima T, Nadano D, Flint D, Matsuda T.

    Biol. Reprod.   Vol. 82   page: 44-53   2010

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  52. O-GlcNAc modification on EGF domains of Notch receptors.

    Sakaidani Y, Furukawa K, Okajima T.

    Methods Enzymol.   Vol. 480   page: 355-73   2010

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  53. Proteomic Analysis of Rodent Ribosomes Revealed Heterogeneity Including Ribosomal Proteins L10-like, L22-like 1, and L39-like. Reviewed

    Sugihara Y, Honda H, Iida T, Morinaga T, Hino S, Okajima T, Matsuda T, Nadano D.

    J. Proteome Res.   Vol. 9   page: 1351-66   2010

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  54. IgG2 dominancy and carbohydrate recognition specificity of C3H/He mouse antibodies directed to cross-reactive carbohydrate determinants (CCDs) bearing ß-(1,2)-xylose and α-(1,3)-fucose

      Vol. 133   page: 28-34   2010

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  55. Roles of glycosylation in Notch signaling.

      Vol. 92   page: 131-164   2010

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  56. Binding of Norovirus virus-like particles (VLPs) to human intestinal Caco-2 cells and the sup-pressive effect of pasteurized bovine colostrum on this VLP binding.

      Vol. 74   page: 541-547.   2010

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  57. Identification of heterogeneous nuclear ribonucleoprotein A/B as a cytoplasmic mRNA-binding protein in early involution of the mouse mammary gland.

      Vol. 28   page: 321-328   2010

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  58. Glycoconjugate glycosyltransferases. Invited Reviewed

    Furukawa K, Tsuchida A, Okajima T, Furukawa K.

    Glycoconj. J.   Vol. 26   page: 987-998   2009

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  59. Periodate-resistant carbohydrate epitopes recognized by IgG and IgE antibodies from some of the immunized mice and patients with allergy. Reviewed

    Hino S, Matsubara T, Urisu A, Aoki N, Sato C, Okajima T, Nadano D, Matsuda T.

    Biochem. Biophys Res. Commun.   Vol. 380   page: 632-637   2009

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  60. Contributions of chaperone and glycosyltransferase activities of O-fucosyltransferase 1 to Notch signaling Reviewed

    Okajima T, Reddy B, Matsuda T and Irvine KD

    BMC biology   Vol. 6 ( 1 ) page: 1-26   2008.1

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  61. Biological functions of glycosyltransferase genes involved in O-fucose glycan synthesis Invited Reviewed

    Okajima T, Matsuura A, Matsuda T

    J. Biochem.   Vol. 144   page: 1-6   2008

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  62. *O-linked GlcNAc is present on the extracellular domain of Notch receptors. Reviewed

    Matsuura A, Ito M, Sakaidani Y, Kondo T, Murakami K, Furukawa K, Nadano D, Matsuda T, and Okajima T

    J. Biol. Chem.   Vol. 283 ( 51 ) page: 35486-35495   2008

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  63. Glycosyltransferases involved in O-fucose glycan synthesis.

    Okajima T, Matsuda T

    Experimental Glycoscience     page: 33-35   2008

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  64. 糖転移酵素のNotch受容体フォールディングにおける役割

    松浦愛子・松田幹・岡島徹也

    蛋白質核酸酵素   Vol. 53   page: 1480-1485   2008

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  65. Serum and monoclonal IgE antibodies from NC/Nga mice with severe atopic-like dermatitis recognize an autoantigen, histone H3. Reviewed

    Matsubara T, Aoki N, Hino H, Okajima T, Nadano D, Matsuda T

    Clin. Exp. Allergy   Vol. 39   page: 579-590   2008

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    Language:English   Publishing type:Research paper (scientific journal)  

  66. Absorption, Migration and Kinetics in Peripheral Blood of Orally Administered Ovalbumin in a Mouse Model Reviewed

    Matsubara T, Aoki N, Honjoh T, Mizumachi K, Kurisaki JI, Okajima T, Nadano D, Matsuda T

    Biosci. Biotechnol. Biochem.   Vol. 72   page: 2555-2565   2008

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  67. Suppressive expression of the glutelin A1-collagen peptide fusion gene in hybrid rice lines with the mutant line, Low Glutelin Content-1 (LGC-1) Reviewed

    Hashizume F, Hino S, Okajima T, Nadano D, Aoki N and Matsuda T

    Plant Biotechnol   Vol. 25   page: 465-471   2008

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  68. Development and evaluation of transgenic rice seeds accumulating a type II-collagen tolerogenic peptide Reviewed

    Hashizume F, Hino S, Kakehashi M, Okajima T , Nadano D, Aoki N, and Matsuda T

    Transgenic Research   Vol. 17   page: 1117-1129   2008

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  69. Glycoconjugate glycosyltransferases Invited Reviewed

    Furukawa K, Tsuchida A, Okajima T, Furukawa K

    Glycoconj. J   Vol. 26   page: 987-98   2008

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  70. Engineering of a mammalian O-glycosylation pathway in the yeast Saccharomyces cerevisiae: production of O-fucosylated epidermal growth factor domains Reviewed

    Yuko Chigira, Takuji Oka, Tetsuya Okajima and Yoshifumi Jigami

    Glycobiology   Vol. 18   page: 303-314   2008

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  71. Association of chicken zona pellucida glycoprotein (ZP) B1 with ZPC induces formation of ZPB1-ZPC fibrous aggregates containing disulfide-bridged ZPB1 dimer. Reviewed

    Okumura H, Okajima T, Nadano D, Matsuda T.

    Biochem Biophys Res Commun.   Vol. 364 ( 3 ) page: 682-688   2007.12

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  72. Bystin in human cancer cells: intracellular localization and function in ribosome biogenesis. Reviewed

    Miyoshi M, Okajima T, Matsuda T, Fukuda MN, Nadano D.

    Biochem J   Vol. 404 ( 3 ) page: 373-381   2007.6

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  73. Roles of fucosyltransferase and fucose in Notch signaling Invited

    Okajima T, Matuda T.

    Methods Enzymol   Vol. 417   page: 116-26   2006

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  74. *Chaperone activity of protein O-fucosyltransferase 1 promotes notch receptor folding. Reviewed

    Okajima T, Xu A, Lei L, Irvine KD.

    Science   Vol. 307   page: 1599-603   2005.3

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    Notch proteins are receptors for a conserved signaling pathway that affects numerous cell fate decisions. We found that in Drosophila, Protein O-fucosyltransferase 1 (OFUT1), an enzyme that glycosylates epidermal growth factor-like domains of Notch, also has a distinct Notch chaperone activity. OFUT1 is an endoplasmic reticulum protein, and its localization was essential for function in vivo. OFUT1 could bind to Notch, was required for the trafficking of wild-type Notch out of the endoplasmic reticulum, and could partially rescue defects in secretion and ligand binding associated with Notch point mutations. This ability of OFUT1 to facilitate folding of Notch did not require its fucosyltransferase activity. Thus, a glycosyltransferase can bind its substrate in the endoplasmic reticulum to facilitate normal folding.

  75. *Modulation of notch-ligand binding by protein O-fucosyltransferase 1 and fringe. Invited Reviewed

    Okajima T, Xu A, Irvine KD.

    J Biol Chem.   Vol. 278   page: 42340-5   2003.10

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  76. Synthesis of disialyl Lewis a (Le(a)) structure in colon cancer cell lines by a sialyltransferase, ST6GalNAc VI, responsible for the synthesis of alpha-series gangliosides. Reviewed

    Tsuchida A, Okajima T, Furukawa K, Ando T, Ishida H, Yoshida A, Nakamura Y, Kannagi R, Kiso M, Furukawa K.

    J Biol Chem.   Vol. 278   page: 22787-94   2003.6

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  77. XGalT-1 involved in the synthesis of glyosaminoglycans of proteoglycans and Ehlers-Danlos syndrome (progeroid type) Invited

    Furukawa K, Okajima T, Nakamura Y.

    Tanpakushitsu Kakusan Koso.   Vol. 48 ( 8 Suppl ) page: 1152-7   2003.1

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  78. *Regulation of notch signaling by O-linked fucose. Invited Reviewed

    Okajima T, Irvine KD.

    Cell   Vol. 111   page: 893-904   2002.12

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  79. Galactosyltransferase I is a gene responsible for progeroid variant of Ehlers-Danlos syndrome: molecular cloning and identification of mutations. Invited

    Furukawa K, Okajima T.

    Biochim Biophys Acta.   Vol. 1573 ( 3 ) page: 377-81   2002.12

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  80. Identification of a Drosophila gene encoding xylosylprotein beta4-galactosyltransferase that is essential for the synthesis of glycosaminoglycans and for morphogenesis. Reviewed

    Nakamura Y, Haines N, Chen J, Okajima T, Furukawa K, Urano T, Stanley P, Irvine KD, Furukawa K.

    J Biol Chem.   Vol. 277 ( 48 ) page: 46280-8   2002.11

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  81. b-series Ganglioside deficiency exhibits no definite changes in the neurogenesis and the sensitivity to Fas-mediated apoptosis but impairs regeneration of the lesioned hypoglossal nerve. Reviewed

    Okada M, Itoh Mi M, Haraguchi M, Okajima T, Inoue M, Oishi H, Matsuda Y, Iwamoto T, Kawano T, Fukumoto S, Miyazaki H, Furukawa K, Aizawa S, Furukawa K.

    J Biol Chem.   Vol. 277 ( 3 ) page: 1633-6   2002.1

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  82. Expression cloning of human globoside synthase cDNAs: Identification of β3Gal-T3 as UDP-N-acetylgalactosamine: globotriaosylceramide β1,3-N-acetyl-galactosaminyltransferase. Reviewed

    Okajima T, Nakamura Y, Uchikawa M, Haslam DB, Numata Si, Furukawa K, Urano T, Furukawa K

    J. Biol. Chem.   Vol. 275   page: 40498-40503   2000

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  83. Molecular cloning and expression of mouse GD1α/GT1aα/GQ1bα synthase (ST6GalNAc VI) gene. Reviewed

    Okajima T, Chen HH, Ito H, Kiso M, Tai T, Furukawa K, Urano T, Furukawa K.

    J. Biol. Chem.   Vol. 275   page: 6717-6723   2000

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  84. Molecular cloning of Gb3/CD77 synthase, a glycosyltransferase that initiates the synthesis of globo-series glycosphingolipids. Reviewed

    Kojima Y, Fukumoto S, Furukawa K, Okajima T, Wiels J, Yokoyama K, Suzuki Y, Urano T, Ohta M, Furukawa K.

    J. Biol. Chem.   Vol. 275   page: 15152-15156   2000

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  85. Assignment of human xylosylprotein beta-1,4-galactosyltransferase gene (B4GALT7) to human chromosome 5q35.2-->q35.3 by in situ hybridization. Reviewed

    Kuroiwa A, Matsuda Y, Okajima T, Furukawa K

    Cytogenet. Cell Genet.   Vol. 89   page: 8-9   2000

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  86. Molecular basis for the p phenotype: Identification of distinct and multiple mutations in the α1,4-galactosyltransferase gene in Swedish and Japanese individuals. Reviewed

    Furukawa K, Iwamura K, Uchikawa M, Sojka BN, Wiels J, Okajima T, Urano T, Furukawa K.

    J. Biol. Chem.   Vol. 275   page: 37752-37756   2000

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  87. Molecular cloning of brain-specific GD1α synthase (ST6GalNAc V) containing CAG/Glutamine repeats. Reviewed

    Okajima T, Fukumoto S, Ito H, Kiso M, Hirabayashi Y, Urano T, Furukawa K, Furukawa K.

    J. Biol. Chem   Vol. 274   page: 30557-30562   1999

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  88. Molecular cloning of a novel α2,3-sialyltransferase (ST3Gal VI) that sialylates type II lactosamine structures on glycoproteins and glycolipids. Reviewed

    Okajima T, Fukumoto S, Miyazaki H, Ishida H, Kiso M, Furukawa K, Urano T, Furukawa K.

    J. Biol. Chem.   Vol. 274   page: 11479-11486   1999

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  89. Human homolog of Caenorhabditis elegans sqv-3 gene is galactosyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans. Reviewed

    Okajima T, Yoshida K, Kondo T, Furukawa K.

    J. Biol. Chem.   Vol. 274   page: 22915-22918   1999

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  90. *Molecular basis for the progeroid variant of Ehlers-Danlos syndrome. Identification and characterization of two mutations in galactosyltransferase I gene. Reviewed

    Okajima T, Fukumoto S, Furukawa K, Urano T, Furukawa K.

    J. Biol. Chem.   Vol. 274   page: 28841-28844   1999

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  91. Nuclear localization of Ca2+/calmodulin-dependent protein kinase IV and calspermin. Reviewed

    Okajima T, Okuno S, Fujisawa H, Hagiwara M.

    Bioimages   Vol. 4   page: 117-128   1996

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  92. RNA priming coupled with DNA synthesis on natural template by calf thymus DNA polymerase α-primase. Reviewed

    Suzuki M, Savoysky E, Izuta S, Tatebe M, Okajima T, Yoshida S.

    Biochemistry   Vol. 32   page: 12782-92   1993

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Books 12

  1. Glycoscience: Biology and Medicine, Editors: Taniguchi N. et al. Extracellular O-GlcNAcylation

    Ogawa M, Furukawa K, Okajima T.( Role: Sole author)

    Springer  2015 

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    Language:Japanese

  2. Handbook of Glycosyltransferases and Related Gene, Editors: Taniguchi N. et al. ST3 β-galactoside α-2,3-sialyltransferase 6 (ST3GAL6)

    Okajima T, and Furukawa, K.( Role: Joint author)

    Springer  2014 

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    Language:English

  3. Handbook of Glycosyltransferases and Related Gene, Editors: Taniguchi N. et al. ST6 N-acetylgalactosaminide α-2,6-sialyltransferase 5,6 (ST6GALNAC5,6)

    Okajima T, and Furukawa, K( Role: Sole author)

    Springer  2014 

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    Language:English

  4. 第三の生命鎖 糖鎖の機能と疾患 編集 門松健治ら 新たに同定されたO-GlcNAc型ドメイン特異糖鎖と生物学的役割

    河合崇生、古川鋼一、岡島徹也( Role: Sole author)

    羊土社  2013 

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    Language:Japanese

  5. Roles of glycosyltransferases in Notch receptor folding

    Aiko Matsuura, Tsukasa Matsuda, Tetsuya Okajima( Role: Joint author)

    2008 

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    Language:Japanese

  6. Experimental Glycoscience, Editors: Taniguchi, N. et al. Glycosyltransferases involved in O-fucose glycan synthesis.

    Okajima T, Matsuda T.( Role: Joint author)

    Elsevier  2008 

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    Language:English

  7. EGFドメインに見いだされる新型糖鎖と生体機能制御

    岡島徹也( Role: Sole author)

    化学と生物  2006.12 

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  8. 未来を拓く糖鎖科学

    岡島徹也 古川鋼一( Role: Joint author)

    金芳社  2005.12 

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  9. O-フコース型糖鎖によるNotchシグナル制御の分子機構

    岡島徹也( Role: Sole author)

    実験医学  2004 

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  10. プロテオグリカンの糖鎖の合成にかかわるXgalT-1とEhlers-Danlos症候群(早老型)

    古川鋼一・岡島徹也・中村陽子( Role: Joint author)

    蛋白質核酸酵素  2003 

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  11. O-フコース型糖鎖によるNotchシグナルの制御

    岡島徹也( Role: Sole author)

    医学のあゆみ  2003 

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  12. ガングリオシドGD3と増殖・アポトーシスシグナル

    古川鋼一,福本 敏,井上雅博,岡田雅彦,大石秀人,岡島徹也,古川圭子( Role: Joint author)

    細胞工学  2001 

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MISC 5

  1. Exploring the significance of xylosyl-extension of O-glucose glycans on EGF repeats for Notch signaling in mammals

    Saiki Wataru, Urata Yusuke, Senoo Yuya, Tsukamoto Yohei, Ma Chenyu, Okajima Tetsuya, Takeuchi Hideyuki

    GLYCOBIOLOGY   Vol. 28 ( 12 ) page: 1028-1029   2018.12

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    Web of Science

  2. Roles of ganglioside GD3 in the regulation of microenvironment of gliomas

    Zhang Pu, Ohkawa Yuki, Ohmi Yuhsuke, Robiul Bhuiyan H., Kato Akira, Furukawa Keiko, Okajima Tetsuya, Wakabayashi Toshihiko, Furukawa Koichi

    CANCER SCIENCE   Vol. 109   page: 262-262   2018.12

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    Web of Science

  3. Significant roles of O-glucose glycans in mammalian Notch trafficking and signaling

    Takeuchi Hideyuki, Yu Hongjun, Hao Huilin, Urata Yusuke, Senoo Yuya, Tsukamoto Yohei, Saiki Wataru, Takeuchi Megumi, Ito Atsuko, Li Huilin, Okajima Tetsuya, Haltiwanger Robert S.

    GLYCOBIOLOGY   Vol. 28 ( 12 ) page: 1017-1018   2018.12

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    Web of Science

  4. Roles of asialo-series ganglioside GD1alpha in human cancer cell lines

    Bhuiyan Robiul H., Kondo Yuji, Ohkawa Yuki, Ohmi Yuhsuke, Zhang Pu, Okajima Tetsuya, Furukawa Keiko, Furukawa Koichi

    CANCER SCIENCE   Vol. 109   page: 877-877   2018.12

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    Web of Science

  5. Ganglioside GD3/GD2 enhance malignant properties of human glioma U251 cells

    Zhang Pu, Iwasawa Taiji, Ohkawa Yuki, Bhuiyan R. H., Momota Hiroyuki, Wakabayashi Toshihiko, Ohmi Yuhsuke, Okajima Tetsuya, Furukawa Keiko, Furukawa Koichi

    CANCER SCIENCE   Vol. 109   page: 256-256   2018.1

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    Web of Science

Presentations 19

  1. Structure and function of extracellular O-GlcNAc Invited International conference

    Tetsuya Okajima and Mitsutaka Ogawa

    10th ACGG Conference 

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    Event date: 2018.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  2. Notch受容体糖鎖情報トラジェクトリーの理解に向けた細胞外O-GlcNAc修飾の構造機能解析 Invited

    岡島 徹也, 竹内 英之, 小川 光貴

    第91回日本生化学会大会 

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    Event date: 2018.9

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Country:Japan  

  3. O-グルコース糖鎖のキシロシル化の Notch シグナルにおける役割の解析 International conference

    浦田 悠輔, 斎木 颯, 妹尾 勇弥, 竹内 英之, 岡島 徹也, 日比 英晴

    第91回日本生化学会大会 

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    Event date: 2018.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  4. 哺乳動物Notch1の上皮成長因子様リピートを修飾するO-GlcNAc糖鎖の構造多様性

    小川 光貴 、妹尾 勇弥、池田 和貴、竹内 英之 、岡島 徹也

    第37回日本糖質学会年会 

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    Event date: 2018.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  5. O-GlcNAc は Notch 受容体 EGF20 の安定性を増強する International conference

    小川光貴, 坂口大和, 矢木宏和, 加藤晃一, 竹内英之, 岡島徹也

    日本生化学会中部支部第82回例会・シンポジウム 

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    Event date: 2018.5

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  6. Roles of N-Glycans on EGF domain-specific O-GlcNAc transferase (EOGT)-catalyzed Notch1 O-GlcNAcylation and Notch signaling International conference

    Sayad Md. Didarul Alam, Mitsutaka Ogawa, Hideyuki Takeuchi and Tetsuya Okajima

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    Event date: 2018.5

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  7. Roles of ganglioside GD3 in the regulation of microenvironment of gliomas

    Zhang P,Ohkawa Y, Momota H, Wakabayashi T, Ohmi Y, Bhuiyan RH, Furukawa Keiko,Okajima Tetsuya, Furukawa Koichi.

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    Event date: 2017.12

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  8. 細胞外O-GlcNAcの修飾に関わるEOGT変異マウスの表現型解析 International conference

    澤口 翔伍、小川 光貴、矢木 宏和、加藤 晃一、岡島 徹也

    2017年度生命科学系学会合同年次大会 

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    Event date: 2017.12

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  9.  脳血管内皮細胞分化におけるNotch受容体O-GlcNAc修飾の役割 International conference

    平泉 光佑、澤口 翔伍、岡島 徹也

    2017年度生命科学系学会合同年次大会 

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    Event date: 2017.12

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  10. ガングリオシドGD3によるグリオーマの腫瘍微小環境の制御機構 Invited International conference

    Zhang P,Ohkawa Y, Momota H, Wakabayashi T, Ohmi Y, Bhuiyan RH, Furukawa Keiko,Okajima Tetsuya, Furukawa Koichi.

    2017年度生命科学系学会合同年次大会 

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    Event date: 2017.12

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  11. Mass Spectrometric analysis of O-GlcNAcylation on Notch EGF and function of N-Glycosylations on EGF domain-specific O-GlcNAc transferase (EOGT) International conference

    Sayad Md. Didarul Alam, Mitsutaka Ogawa, Hideyuki Takeuchi and Tetsuya Okajima

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    Event date: 2017.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  12. Requirement of O-fucosyltransferases for Developmental Processes International conference

    GlycoT 2006 

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    Event date: 2006.6

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  13. Chaperone activity of Protein O-fucosyltransferase I promotes Notch receptor folding. International conference

    HFSP 4th Awardees Annual Meeting 

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    Event date: 2005.6

    Language:English   Presentation type:Oral presentation (general)  

  14. Chaperone activity of Protein O-fucosyltransferase I within the endoplasmic reticulum promotes folding of the Notch receptor.

    Gordon Conference 

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    Event date: 2005.3

    Language:English   Presentation type:Oral presentation (invited, special)  

  15. Chaperone activity of Protein O-fucosyltransferase I promotes Notch receptor folding. International conference

    46th Annual Drosophila Research Conference 

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    Event date: 2005.3

    Language:English   Presentation type:Poster presentation  

  16. Action of Protein O-fucosyltransferase 1 within the endoplasmic reticulum in maturation of the Notch receptor

    US/Japan Glyco 

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    Event date: 2004.11

    Language:English  

  17. Chaperone activity of Protein O-fucosyltransferase I within the endoplasmic reticulum promotes folding of the Notch receptor. International conference

    GlycoT 2004 

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    Event date: 2004.11

    Language:English   Presentation type:Oral presentation (general)  

  18. Modulation of Notch-lingad binding by protein O-fucosyltransferase and fringe International conference

    HFSP 4th Awardees Annual Meeting 

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    Event date: 2004.5

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  19. Modulation of Notch-lingad binding by protein O-fucosyltransferase and fringe International conference

    45th Annual Drosophila Research Conference 

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    Event date: 2004.3

    Language:English   Presentation type:Poster presentation  

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Research Project for Joint Research, Competitive Funding, etc. 6

  1. Notch受容体糖鎖コードの時空間情報解読に向けたin vivoレポーターシステムの構築

    2018.10 - 2019.9

    自然科学研究助成 

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    Grant type:Competitive

  2. 糖転移酵素EOGTによるNotchシグナルと血管形成の制御機構の解明

    2018.4 - 2019.3

    研究助成 

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    Grant type:Competitive

  3. 糖転移酵素のよるNotch受容体の構造•機能の制御機構

    2007.4 - 2008.3

    武田科学振興財団 一般研究奨励 

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    Grant type:Competitive

  4. EGFドメイン特異的翻訳後修飾であるO-フコース/O-グルコース型糖鎖により制御を受ける新規シグナル関連タンパク質の探索

    2007.4 - 2008.3

  5. Control of Notch receptor structure and function by glycosyltransferases

    2006.6 - 2009.5

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    Grant type:Competitive

  6. EGFドメイン特異的糖転移酵素のよるNotch受容体の 構造•機能の調節機構

    2006.4 - 2007.3

    中島記念国際交流財団 日本人若手研究者研究助成金 

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    Grant type:Competitive

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KAKENHI (Grants-in-Aid for Scientific Research) 13

  1. 細胞外O-GlcNAc修飾のNotchシグナルと血管形成における役割

    2015.4 - 2017.3

    科学研究費補助金  基盤研究(B)

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    Authorship:Principal investigator 

  2. Notch シグナルとヘキソサミン経路を介した血液脳関門の制御

    2015.4 - 2017.3

    科学研究費補助金 

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    Authorship:Principal investigator 

  3. 小胞体GlcNAc修飾の神経組織での役割

    2014.4 - 2016.3

    科学研究費補助金  新学術領域研究[公募研究]

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    Authorship:Principal investigator 

  4. モデル生物を活用した先天性脳疾患関連オーファン糖転移酵素の機能解明

    2013.4 - 2015.3

    科学研究費補助金 

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    Authorship:Principal investigator 

  5. 神経組織の機能発現に関与する新規ドメイン特異糖鎖の解析

    2012.4 - 2014.3

    科学研究費補助金  新学術領域研究[公募研究]

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    Authorship:Principal investigator 

  6. 上皮成長因子様ドメインに特徴的な新規翻訳後修飾の同定と修飾機構の解析

    2009.4 - 2011.3

    科学研究費補助金  若手研究(B)

    岡島徹也

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    Authorship:Principal investigator 

    科学研究費補助金 若手研究(B) 403万円

  7. Ofut1によるNotch受容体の構造・機能の調節機構

    2006.4 - 2009.3

    科学研究費補助金  若手研究(A)

    岡島 徹也

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    Authorship:Principal investigator 

  8. 糖転移酵素群によるNOTCHタンパク質の分泌・分解の仕分け機構の解明

    Grant number:22H02815  2022.4 - 2025.3

    科学研究費助成事業  基盤研究(B)

    岡島 徹也

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    Authorship:Principal investigator 

    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

  9. 加齢に伴う運動能力低下におけるNotch1上の細胞外O-GlcNAc機能の解明

    Grant number:20F20410  2020.11 - 2023.3

    科学研究費助成事業  特別研究員奨励費

    岡島 徹也, LO PEIWEN

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    Authorship:Other 

    老化は、骨格筋のエネルギー産生の低下や筋肉量の減少を引き起こす。骨格筋では、1000以上のO-GlcNAc化タンパク質が同定されており、OGTによるPGC-1αのO-GlcNAc化はPGC-1αを安定化し、ミトコンドリア遺伝子の転写を促進することで筋萎縮を抑制し、エネルギー代謝を向上する。一方、骨格筋におけるEOGTによる細胞外O-GlcNAc化の役割は不明である。EOGTはNotch受容体をO-GlcNAc化することで、リガンド依存的なNOTCHシグナルを活性化することが知られている。本研究では、Notch1のO-GlcNAc修飾による筋運動能力の低下のメカニズムについて検証する。
    老化は、骨格筋のエネルギー産生の低下や筋肉量の減少を引き起こし、高齢者の運動能力や生活の質に影響を与える。PGC-1αは転写コアクチベーターであり、骨格筋ではミトコンドリア遺伝子の転写を促進することで筋萎縮を抑制し、エネルギー代謝を向上する。骨格筋では、1000以上のO-GlcNAc化タンパク質が同定されており、OGTによるPGC-1αのO-GlcNAc化はPGC-1αを安定化する。一方、骨格筋におけるEOGTによる細胞外O-GlcNAc化の役割は不明である。EOGTはNotch受容体をO-GlcNAc化することで、リガンド依存的なNOTCHシグナルを活性化する。さらに、PGC-1α発現はNotchシグナルにより制御されることが報告されている。本研究では、Notch1のO-GlcNAc修飾によるPGC-1αの発現制御が加齢に伴う筋運動能力の低下のメカニズムに関与する可能性について検証することを目的とした。本年度は、EOGTの発現様式について、特異抗体を用いた前脛骨筋の免疫組織染色を実施した結果、筋組織に一様に分布するのではなく、特定の筋線維に高い発現が認められた。また、筋線維の分布を野生型マウスを比較したところ、顕著な違いは認められなかった一方で、小型の筋線維の増加と中型の筋線維の減少が認められた。また、ロータロッド試験による筋力の測定を実施した結果、野生マウスと比較してEOGT欠損マウスでは、スコアの低下傾向が認められた。引き続き、EOGT欠損マウスにおける筋力を週齢を追って測定する予定である。
    Eogtの発現様式と筋線維の細胞レベルでの解析より、Eogtの筋線維における役割が改めて示唆される結果が得られるなど、研究計画段階で想定されていたデータが得られている。これらの結果をもとに、今後の研究計画も提案通り進めることができるため、おおむね順調に進展していると判断できる。
    前年度の研究から、ロータロッド試験による筋力の測定を実施した結果、野生マウスと比較して、EOGT欠損マウスを用いて、スコアの低下傾向 が認められた。引き続き、EOGT欠損マウスにおける筋力を週齢を追って測定する。また、EOGT特異抗体を用いた前脛骨筋の組織染色により、EOGTのタンパク質発現が、筋組織に一様に分布するのではなく、タイプIIAを含む一部の筋線維に発現していた。Eogt欠損マウスにおける筋線維の分布の変化が、タイプIIAなど特定の筋線維における変化なのか、それとも全体的な変化であるか明らかにするために、筋線維マーカーとLam inin 2αの組織染色により検証する。また、EOGTの機能を細胞レベルにて明らかにするために、EOGT欠損C2C12細胞を作成し、分化させた細胞における遺伝子発現様式の違いを明らかにする。さらに、EOGTの基質候補して、NOTCH受容体に加えて、DLK1の可能性を検証するために、DLK1のO-GlcNAc糖鎖修飾様式と分子機能における役割を明らかにする。

  10. Integrated analysis of atypical glycosylation as a basis for precise regulation of Notch signaling in the vascular endothelium

    Grant number:19H03416  2019.4 - 2022.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Principal investigator 

    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

  11. O-グルコース糖鎖修飾による筋衛星細胞におけるNotchシグナルの制御機構の解明

    Grant number:19H03176  2019.4 - 2022.3

    科学研究費助成事業  基盤研究(B)

    竹内 英之, 岡島 徹也

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    Authorship:Coinvestigator(s) 

    ヒトの筋肉の再生と恒常性維持の分子制御機構は未だに理解されていない。遺伝性筋疾患である筋ジストロフィーの有病率は、人口10万人あたり20人程度と推定され、有効な治療法は存在しない。研究代表者は、Notch受容体のO-グルコース糖鎖修飾の異常により、筋肉の幹細胞である衛星細胞の数の減少と衛星細胞におけるNotchシグナルの低下が起こり、このことが、成人後に発症する肢帯型筋ジストロフィーの原因となることを見出した [Cell 2008, EMBO Mol Med 2016]。衛星細胞におけるNotchシグナルのO-グルコース糖鎖修飾による調節機構を明らかにすることが本研究の目的である。
    私たちは、次に示すような背景に基づいて本研究プロジェクトを開始した。ヒトの筋肉の再生と恒常性維持の分子機構は未だに理解されていない。遺伝性筋疾患である筋ジストロフィーの有病率は、人口10万人あたり20人程度と推定され、有効な治療法は存在しない。研究代表者は、Notch受容体のO-グルコース糖鎖修飾の異常により、筋肉の幹細胞である衛星細胞の数の減少と衛星細胞におけるNotchシグナルの低下が起こり、このことが、成人後に発症する肢帯型筋ジストロフィーの原因となることを見出した [Cell 2008, EMBO Mol Med 2016]。衛星細胞におけるNotchシグナルのO-グルコース糖鎖修飾による調節機構を明らかにすることが本研究の目的である。細胞生物学的手法により、O-グルコース糖鎖のNotch受容体選択性を調べる。遺伝学的手法を駆使した、世界初の糖鎖レポーターマウスを作製し、質量分析計を用いてNotch受容体上の糖鎖修飾の全貌を明らかにする。
    本年度は、細胞生物学的手法により、ヒト培養細胞株における Notch 受容体の細胞内挙動に対する O-グルコース糖鎖変容の影響を観察した。また、Notch 受容体の細胞外部位に起こる糖鎖修飾を、質量分析計を用いた分子量の精密な分析により明らかにした。以上の実験データを論文としてまとめ投稿した。Notch 受容体機能の糖鎖修飾による制御機構に関する原著論文3 報、並びに、総説 2 報の発表に貢献した。
    研究代表者は、研究成果について、アメリカ糖鎖生物学会においてポスター発表、第 92 回日本生化学会大会において招待口頭発表、日本筋学会第 5 回学術集会において招待口頭発表、第 7 回若手による骨格筋細胞研究会において招待口頭発表を行った。
    課題1: NOTCH2およびNOTCH3の細胞外ドメインに O-グルコース糖鎖修飾が起こるか、そして、O-グルコース糖鎖修飾がNOTCH2およびNOTCH3 の活性化に必要であるか。研究代表者竹内が担当。HEK293T細胞にマウスNOTCH2の細胞外ドメインを発現させ、Ni-NTAアガロースカラムにより精製し、プロテアーゼにより消化後、Fusion LC-MS/MS (Thermo Fisher) にて解析した。NOTCH2 の細胞外部位に 36 個存在する上皮増殖因子様 (EGF) ドメインのうち、O-グルコース糖鎖付加のコンセンサス配列を有するEGF ドメインは、17 個存在する。17 箇所すべての O-グルコース糖鎖の種類とその割合を決定した。
    課題 2: NOTCH1のEGF10に見出された新奇O-結合型糖鎖の性状解析とその生合成を担う糖転移酵素の同定。研究代表者竹内が担当。糖鎖構造解析は研究協力者の青木がジョージア大学で遂行。NOTCH1 EGF10 の O-グルコース修飾部位であるセリン378をアラニンに置換した。その結果、新奇糖鎖と従来型糖鎖の両方が消失することが確認された。リンケージ特異的なグリコシダーゼを用いた解析により、グルコースには beta1-4 結合でガラクトースが結合していることが示唆された。
    課題3: Notch1糖鎖レポーターマウスを作製し、衛星細胞に発現したNotch1上のin vivo における糖鎖修飾を明らかにすること。研究代表者竹内と研究分担者岡島が担当。Bip分泌シグナル配列の直後にFLAGタグを挿入したNotch1 (FLAG-Notch1) が、テトラサイクリン応答因子 (TRE) の作用によって発現誘導されるベクターを作製し、マウス受精卵へのマイクロインジェクションと、偽妊娠させたマウスの卵管内への移植を終えた。
    課題1: NOTCH2およびNOTCH3の細胞外ドメインに O-グルコース糖鎖修飾が起こるか、そして、O-グルコース糖鎖修飾がNOTCH2およびNOTCH3 の活性化に必要であるか。研究代表者竹内が担当。NOTCH3のO-グルコース糖鎖修飾を上と同様に解析する。HEK293T細胞にて、POGLUT1、GXYLT1、GXYLT2、XXYLT1を個々にノックアウトした細胞、およびGXYLT1とGXYLT2の両者をノックアウトした細胞を用いて、DLL1リガンド依存的なNOTCH2およびNOTCH3シグナルレポーターアッセイと、HEK293T細胞でNotchシグナル活性化の指標となる下流の標的遺伝子の発現レベルの解析を行う。
    課題 2: NOTCH1のEGF10に見出された新奇O-結合型糖鎖の性状解析とその生合成を担う糖転移酵素の同定。 研究代表者竹内が担当。糖鎖構造解析は研究協力者の青木がジョージア大学で遂行。化学的手法を用いて、新奇糖鎖構造の完全解明を試みる。新奇糖鎖修飾を担う糖転移酵素を同定するために、上で決定した糖鎖構造に基づいて、基質特異性から生合成を担う糖転移酵素遺伝子は、B4GALT 群に属することが推定された。そこで、コペンハーゲン大学Clausen博士らの作製した糖転移酵素遺伝子欠損HEK293 細胞株を入手し、NOTCH1を発現させ、質量分析により新奇糖鎖修飾が消失するか調べる。
    課題3: Notch1糖鎖レポーターマウスを作製し、衛星細胞に発現したNotch1上のin vivo における糖鎖修飾を明らかにすること。研究代表者竹内と研究分担者岡島が担当。マイクインジェクションにより得られた子マウスの離乳後、尻尾より DNA を抽出し、PCR 法により導入遺伝子の検定を行う。胎児由来線維芽細胞を用いて、Notch1 タンパク質の発現誘導実験を行う。

  12. Roles of Notch signaling and hexosamine pathway on regulation of blood brain barrier

    Grant number:15K15064  2015.4 - 2018.3

    OKAJIMA Tetsuya

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    Authorship:Principal investigator 

    Grant amount:\3770000 ( Direct Cost: \2900000 、 Indirect Cost:\870000 )

    Notch receptors are modified with unique post-translational modifications on epidermal growth (EGF)-like repeats. Previous studies elucidated the presence of O-GlcNAc modification and O-GlcNAc transferase, EOGT. O-GlcNAc modification by EOGT regulates DLL4-mediated Notch1 activation. In this study, we investigated roles of O-GlcNAc-mediated Notch regulation on integrity of blood vessels, which is pivotal for blood brain barrier. In Eogt-deficient mice, extravasation of biotin derivatives and deposition of fibrinogen were detected. Similar phenotype was observed in endothelial deletion of EOGT. In addition to N-cadherin, expression of components of tight junction were decreased, suggesting that EOGT-dependent Notch signaling represents a novel mechanism for regulation of blood vessels integrity.

  13. Roles of extracellular O-GlcNAc on Notch signaling and vascular development

    Grant number:26291020  2014.4 - 2018.3

    OKAJIMA Tetsuya

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    Authorship:Principal investigator 

    Grant amount:\16640000 ( Direct Cost: \12800000 、 Indirect Cost:\3840000 )

    Notch receptors are modified with unique post-translational modifications on epidermal growth (EGF)-like repeats at the extracellular domains. Previous studies revealed that besides O-fucose and O-glucose O-GlcNAc modification occurs on EGF repeats. However, biological function of O-GlcNAc on Notch receptors remained unknown. In this study, EOGT, a glycosyltransferase catalyzing O-GlcNAc modification of EGF domains, is inactivated in mice and phenotypical analyses were performed. Results revealed that specific EGF domains of Notch1 are modified with O-GlcNAc, which regulated DLL4-mediated Notch1 activation and thus Notch-dependent vascular development in the retina.

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Teaching Experience (On-campus) 6

  1. 生物の化学

    2015

  2. 生物学基礎I

    2015

  3. 大学院 基盤医科学実習

    2015

  4. 基礎医学セミナー

    2015

  5. 生化学実習

    2015

  6. 人体機能学

    2015

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