Studies of functional glycans on alfa-dystroglycan associated with congenital muscular dystrophies

• Project/Area Number: 26291021
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kyoto University
• Principal Investigator: Oka Shogo 京都大学, 医学(系)研究科(研究院), 教授 (60233300)
• Co-Investigator(Kenkyū-buntansha): 竹松 弘 京都大学, 医学(系)研究科(研究院), 准教授 (80324680) ; 森瀬 譲二 京都大学, 医学(系)研究科(研究院), 助教 (60755669)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: ジストログリカン / 先天性筋ジストロフィー / O-マンノース型糖鎖 / 糖転移酵素 / ラミニン結合性糖鎖 / ラミニン / POMGnT2/AGO61 / 神経初期発生 / ポストリン酸糖鎖

Outline of Final Research Achievements

α-Dystroglycan (α-DG) is a cell surface glycoprotein that serves as a receptor for extracellular matrix components such as laminin. The α-DG-ligand interaction is mediated by a unique O-mannose-linked glycan attached to α-DG, and the glycosylation deficiency of α-DG causes several forms of congenital muscular dystrophies associated with cobblestone lissencephaly, classified as dystroglycanopathy. In this study, we investigated the regulatory mechanism for the unique O-mannose-linked glycan expression. We also revealed initial pathological events in the developing brain of Pomgnt2-knockout mouse as a dystroglycanopathy model.

Research Products

• [Journal Article] Dystroglycan glycosylation: structure, synthetic pathway, and in vivo role in the brain development (2016)
  • Author(s): Nakagawa N and Oka S
  • Journal Title: 生化学 Volume: 88 Issue: 4 Pages: 488-491
  • DOI: 10.14952/SEIKAGAKU.2016.880488
  • NAID: 40020948090
  • ISSN: 0037-1017
  • Year and Date: 2016-08-25
  • Peer Reviewed
• [Journal Article] Ghrelin O-acyltransferase knockout mice show resistance to obesity when fed high-sucrose diet. (2016)
  • Author(s): T. Kouno, N. Akiyama, T. Ito, T. Okuda, I. Nanchi, M. Notoya, S. Oka and H. Yukioka
  • Journal Title: J Endocrinol. Volume: 228 Issue: 2 Pages: 115-125
  • DOI: 10.1530/joe-15-0330
  • Peer Reviewed
• [Journal Article] Reduced intake of carbohydrate prevents the development of obesity and impaired glucose metabolism in ghrelin O-acyltransferase knockout mice. (2016)
  • Author(s): Kouno T, Akiyama N, Fujieda K, Nanchi I, Okuda T, Iwasaki T, Oka S, Yukioka H.
  • Journal Title: Peptides Volume: 86 Pages: 145-152
  • DOI: 10.1016/j.peptides.2016.11.003
  • Peer Reviewed
• [Journal Article] Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow. (2016)
  • Author(s): Watanabe H, Okahara K, Naito-Matsui Y, Abe M, Go S, Inokuchi J, Okazaki T,Kobayashi T, Kozutsumi Y, Oka S, Takematsu H.
  • Journal Title: Mol Biol Cell. Volume: 27 Issue: 13 Pages: 2037-2050
  • DOI: 10.1091/mbc.e15-08-0555
  • Peer Reviewed / Open Access
• [Journal Article] A sulfated glycosaminoglycan linkage region is a novel type of Human Natural Killer-1 (HNK-1) epitope expressed on aggrecan in perineuronal nets. (2015)
  • Author(s): Yabuno, K., Morise, J., Kizuka, Y., Hashii, N., Kawasaki N., Takahashi, S., Miyata, S., Izumikawa, T., Kitagawa, H., Takematsu, H., and Oka, S.
  • Journal Title: PLoS ONE, Volume: 10 Issue: 12 Pages: e0144560-e0144560
  • DOI: 10.1371/journal.pone.0144560
  • NAID: 120007128471
  • Peer Reviewed / Open Access
• [Journal Article] Role of Site-Specific N-Glycans Expressed on GluA2 in the Regulation of Cell Surface Expression of AMPA-Type Glutamate Receptors. (2015)
  • Author(s): Y. Takeuchi, J. Morise, I. Morita, H. Takematsu, and S. Oka
  • Journal Title: PLoS One Volume: 10 Issue: 8 Pages: e0135644-e0135644
  • DOI: 10.1371/journal.pone.0135644
  • NAID: 120005678163
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ectopic clustering of Cajal-Retzius and subplate cells is an initial pathological feature in Pomgnt2-knockout mice, a model of dystroglycanopathy (2015)
  • Author(s): Naoki Nakagawa, Hirokazu Yagi, Koichi Kato, Hiromu Takematsu, and Shogo Oka
  • Journal Title: Sci. Rep. Volume: 5 Issue: 1 Pages: 11163-11163
  • DOI: 10.1038/srep11163
  • NAID: 120005670888
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Loss of α1,6-fucosyltransferase decreased hippocampal long-term potentiation: implications for core fucosylation in the regulation of AMPA receptor heteromerization and cellular signaling. (2015)
  • Author(s): Gu, W., Fukuda, T., Isaji, T., Hang, Q., Lee, H., Sakai, S., Morise, J., Mitoma, J., Higashi, H., Taniguchi, N., Yawo, H., Oka, S. and Gu, J.
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 28 Pages: 17566-75
  • DOI: 10.1074/jbc.m114.579938
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Major glycan structure underlying expression of the Lewis X epitope in the developing brain is O-mannose-linked glycans on phosphacan/RPTPβ (2015)
  • Author(s): Shohei Yaji, Hiroshi Manya, Naoki Nakagawa, Hiromu Take matsu, Tamao Endo, Reiji Kannagi, Toru Yoshihara, Masahide Asano, Shogo Oka
  • Journal Title: Glycobiology Volume: 25 Issue: 4 Pages: 376-385
  • DOI: 10.1093/glycob/cwu118
  • Peer Reviewed / Open Access
• [Journal Article] Binding specificity of anti-HNK-1 IgM M-protein in anti-MAG neuropathy: Possible clinical relevance. (2015)
  • Author(s): Hamada Y, Hirano M, Kuwahara M, Samukawa M, Takada K, Morise J, Yabuno K, Oka S, and Kusunoki S.
  • Journal Title: Neurosci Res. Volume: 91 Pages: 63-68
  • DOI: 10.1016/j.neures.2014.09.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] α-Klotho mice demonstrate increased expression of the non-sulfated N-glycan form of the HNK-1 glyco-epitope in kidney tissue. (2014)
  • Author(s): K. Akasaka-Manya, H. Manya, Y. Kizuka, S. Oka and T. Endo
  • Journal Title: J. Biochem. Volume: 156 Issue: 2 Pages: 107-113
  • DOI: 10.1093/jb/mvu024
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fpk1/2 kinases regulate cellular sphingoid long-chain base (LCB) abundance and alter cellular resistance to LCB elevation or depletion. (2014)
  • Author(s): Yamane-Sando Y, Shimobayashi E, Shimobayashi M, Kozutsumi Y, Oka S, Takematsu H.
  • Journal Title: Microbiology Open Volume: 3 Issue: 2 Pages: 196-212
  • DOI: 10.1002/mbo3.160
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 胎生期にTenascin-C上に発現するHNK-1糖鎖の機能解析 (2016)
  • Author(s): 中村 綾沙、森瀬 譲二、竹松 弘、岡 昌吾
  • Organizer: 第８９回日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県）
  • Year and Date: 2016-09-25
• [Presentation] AMPA型グルタミン酸受容体サブユニットは神経細胞膜表面上を単量体で拡散する (2016)
  • Author(s): 森瀬 譲二、鈴木 健一、北川 英佳、若園 佳彦、髙宮 考悟、楠見 明弘、竹松 弘、岡 昌吾
  • Organizer: 第８９回日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県）
  • Year and Date: 2016-09-25
• [Presentation] 特定のN型糖鎖がAMPA型グルタミン酸受容体サブユニットGluA1の細胞内輸送を制御する (2016)
  • Author(s): 山本 采季、森瀬 譲二、竹松 弘、岡 昌吾
  • Organizer: 第３５回日本糖質学会年会
  • Place of Presentation: 高知市文化プラザ（高知県）
  • Year and Date: 2016-09-01
• [Presentation] Identification of modifier genes that modulate cell surface P-selectin ligand expression. (2016)
  • Author(s): Hiromu Hakematsu, H. kitagawa, R. Kannagi, and S. Oka
  • Organizer: ICS 2016 (XXVIII Inernatinal Carbohydrate Symposium)
  • Place of Presentation: New Orieans, Louisiana, USA
  • Year and Date: 2016-07-17
  • Int'l Joint Research
• [Presentation] Specific N-glycans regulate cell surface expression of AMPA-type glutamate receptors. (2016)
  • Author(s): J. Morise, S. Yamamoto, N. Hashii, N. Kawasaki, H. Takematsu, and S. Oka
  • Organizer: ICS 2016 (XXVIII Inernatinal Carbohydrate Symposium)
  • Place of Presentation: New Orieans, Louisiana, USA
  • Year and Date: 2016-07-17
  • Int'l Joint Research
• [Presentation] Psychosine-triggered endomitosis to produce multiploid cells. (2016)
  • Author(s): H. Watanabe, T. Kobayashi, J. Inokuchi, T. Okazaki, S. Oka and H. Takematsu
  • Organizer: 2016 Korea-Japan Bioactive Lipid Joint Symposium
  • Place of Presentation: BAREVE Hotel in Jeju island, South Korea
  • Year and Date: 2016-05-11
  • Int'l Joint Research / Invited
• [Presentation] 神経初期発生期における特徴的なHNK-1糖鎖発現に関する研究 (2016)
  • Author(s): 石川 明香里, 籔野 景子, 中川 直樹, 岡 昌吾
  • Organizer: 日本薬学会第１３６年会
  • Place of Presentation: パシフィコ横浜 (神奈川県）
  • Year and Date: 2016-03-26
• [Presentation] Membrane glycosphingolipid modulate psychosine-triggered multiploid cell formation. (2016)
  • Author(s): H. Watanabe, T. Okazaki, T. Kobayashi, S. Oka, and H. Takematsu
  • Organizer: The 3rd International Symposium on Glyco-Neuroscience
  • Place of Presentation: Awaji Yumebutai International Conference Center (Japan)
  • Year and Date: 2016-01-14
  • Int'l Joint Research / Invited
• [Presentation] Single fluorescent molecule tracking approach for AMPA-type glutamate receptor subunits diffusing in cell plasma membranes. (2016)
  • Author(s): i Morise, K. G.N. Suzuki, A. Kitagawa, Y. Wakazono, K. Takamiya, A. Kusumi, H. Takematsu, and S. Oka
  • Organizer: The 3rd International Symposium on Glyco-Neuroscience
  • Place of Presentation: Awaji Yumebutai International Conference Center (Japan)
  • Year and Date: 2016-01-14
  • Int'l Joint Research
• [Presentation] POMGNT1とB3GALNT2は協同的にalpha-ジストログリカン上の部位特異的なリガンド結合糖鎖の発現を制御する (2015)
  • Author(s): 東 良柄, 中川 直樹, 竹松 弘, 岡 昌吾
  • Organizer: BMB２０１５（第８８回日本生化学会大会、第３８回日本分子生物学会年会合同大会）
  • Place of Presentation: 神戸ポートアイランド（兵庫県）
  • Year and Date: 2015-12-01
• [Presentation] 老化に伴って増加する非硫酸化グルクロン酸によるCD13の活性変化 (2015)
  • Author(s): 赤阪－萬谷啓子、萬谷 博 、岡 昌吾 、遠藤玉夫
  • Organizer: 第３４回日本糖質学会年会
  • Place of Presentation: 東京大学（東京都）
  • Year and Date: 2015-07-31
• [Presentation] NMDA型グルタミン酸受容体サブユニットGluN1の糖鎖付加におけるC-末端領域の役割 (2015)
  • Author(s): 小山詩織、黒田真由美、森瀬譲二、岡 昌吾
  • Organizer: 第３４回日本糖質学会年会
  • Place of Presentation: 東京大学（東京都）
  • Year and Date: 2015-07-31
• [Presentation] AGO61, a causative gene for dystroglycanopathy, is required for the maintenance of the basement membrane integrity and neuronal migration (2014)
  • Author(s): Naoki Nakagawa, Hirokazu Yagi, Koichi Kato, and Shogo Oka
  • Organizer: Neuroscience 2014
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] 神経回路形成期におけるホスファカン上の特徴的なO-マンノース型HNK-1糖鎖構造の解析 (2014)
  • Author(s): 森瀬 譲二、木塚 康彦、藪野 景子、殿山 泰弘、橋井 則貴、川崎 ナナ、萬谷 博、鈴木 友子、武田 伸一、遠藤 玉夫、前田 信明、竹松 弘、岡 昌吾
  • Organizer: 第８７回日本生化学会大会
  • Place of Presentation: 京都国際会館 （京都府）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 神経系に発現するLewis X抗原のキャリアタンパク質および生合成酵素の解析 (2014)
  • Author(s): 中川直樹、萬谷 博、家治翔平、竹松 弘、遠藤玉夫、神奈木玲児、吉原 亨、浅野雅秀、岡 昌吾
  • Organizer: 第33回 日本糖質学会年会
  • Place of Presentation: 名古屋大学（愛知県）
  • Year and Date: 2014-08-10 – 2014-08-12
• [Presentation] AGO61はラミニン結合性糖鎖の初期構造の形成に関与する (2014)
  • Author(s): 矢木宏和、中川直樹、齋藤拓也、戸田達史、Sz-Wei Wu、Kay-Hooi Khoo、岡 昌吾、加藤晃
  • Organizer: 第33回 日本糖質学会年会
  • Place of Presentation: 名古屋大学（愛知県）
  • Year and Date: 2014-08-10 – 2014-08-12
• [Presentation] スフィンゴ糖脂質サイコシンによって誘導される多倍体化は、細胞に発現するスフィンゴ糖脂質により正に、スフィンゴミエリンにより負に調節される (2014)
  • Author(s): 渡邉 寛、岡原 京平、小堤 保則、岡 昌吾、竹松 弘
  • Organizer: 第56回 日本脂質生化学会
  • Place of Presentation: 近畿大学（大阪府）
  • Year and Date: 2014-06-06 – 2014-06-07
• [Book] 糖鎖の新機能開発・応用ハンドブック (2015)
  • Author(s): 岡 昌吾
  • Total Pages: 678
  • Publisher: 株式会社NTS
• [Book] Glycoscience: Biology and Medicine (Taniguchi, N., Endo, T., Hart, G.W., Seeberger, P.H., and Wong, C.H., eds) (2015)
  • Author(s): Naoki Nakagawa and Shogo Oka
  • Total Pages: 1568
  • Publisher: Springer
• [Remarks] 岡研究室ホームページ
  • URL: http://oka-lab.hs.med.kyoto-u.ac.jp
• [Remarks] 岡研究室ホームページ
  • URL: http://oka-lab.hs.med.kyoto-u.ac.jp/index.html