Role of glycans in control of FGF23 and Klotho functions

• Project/Area Number: 16K14695
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Kyoto University
• Principal Investigator: Oka Shogo 京都大学, 医学研究科, 教授 (60233300)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: αKlotho / FGF23 / HNK-1糖鎖 / 腎臓 / グルクロン酸転移酵素 / 糖鎖 / αKlothoタンパク質 / O型糖鎖

Outline of Final Research Achievements

αKlotho is predominantly expressed in kidney and has important roles in regulation of mineral metabolism including calcium. αKlotho is also known to act as a co-receptor for fibroblast growth factor 23 (FGF23). Mice lacking functional αKlotho protein exhibit phenotypes resembling human aging. α-Klotho is a type I membrane protein with two glucosidase-like domains in a extracellular region. It is, however, still unclear how these glucosidase-like domains are utilized for the klotho function since the essential glutamate residues for enzymatic activity are not conserved in αKlotho. In this study, we investigated the role of HNK-1 and its related glycans in the functional regulation for FGF23 and αKlotho.

Research Products

• [Journal Article] Ribosomal protein uS7/Rps5 serine-223 in protein kinase-mediated phosphorylation and ribosomal small subunit maturation (2018)
  • Author(s): Tomioka Makoto、Shimobayashi Mitsugu、Kitabatake Makoto、Ohno Mutsuhito、Kozutsumi Yasunori、Oka Shogo、Takematsu Hiromu
  • Journal Title: SCIENTIFIC REPORT Volume: 8 Issue: 1 Pages: 1244-1244
  • DOI: 10.1038/s41598-018-19652-z
  • NAID: 120006510286
  • Peer Reviewed / Open Access
• [Journal Article] The role of human natural killer-1 (HNK-1) carbohydrate in neuronal plasticity and disease. (2017)
  • Author(s): Morise J, Takematsu H, Oka S.
  • Journal Title: Biochim. Biophys. Acta. Volume: 1861 Issue: 10 Pages: 2455-2461
  • DOI: 10.1016/j.bbagen.2017.06.025
  • Peer Reviewed
• [Journal Article] MiR30-GALNT1/2 Axis-Mediated Glycosylation Contributes to the Increased Secretion of Inactive Human Prohormone for Brain Natriuretic Peptide (proBNP) From Failing Hearts. (2017)
  • Author(s): Nakagawa Y, Nishikimi T, Kuwahara K, Fujishima A, Oka S, Tsutamoto T, Kinoshita H, Nakao K, Cho K, Inazumi H, Okamoto H, Nishida M, Kato T, Fukushima H, Yamashita JK, Wijnen WJ, Creemers EE, Kangawa K, Minamino N, Nakao K, Kimura T.
  • Journal Title: J Am Heart Assoc. Volume: 6 Issue: 2
  • DOI: 10.1161/jaha.116.003601
  • NAID: 120007100125
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] 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] 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] 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
• [Presentation] N型糖鎖欠損体によるAMPA型グルタミン酸受容体の機構お解析 (2017)
  • Author(s): 森瀬譲二、鈴木健一、北川 英佳、山本 采季、竹内祐介、楠見明弘、竹松 弘、岡 昌吾
  • Organizer: 第１８回関西グライコサイエンスフォーラム
• [Presentation] AMPA型グルタミン酸受容体のN型糖鎖修飾は、4量体形成と細胞表面への移送を制御する (2017)
  • Author(s): Kandel Babu Munal、緑川 良介、岡 昌吾、川崎 ナナ、髙倉 大輔、髙宮 考悟
  • Organizer: 第４０回日本神経科学大会
• [Presentation] ストレプトゾトシン誘導性腎機能障害マウスにおける非硫酸化型HNK-1糖鎖の発現解析 (2017)
  • Author(s): 北野仁望、森瀬譲二、岡昌吾
  • Organizer: 第５７回日本臨床化学会年次学術集会
• [Presentation] 抗MAG抗体ニューロパチーにおける抗体affinityの継時的変化と臨床経過の比較 (2017)
  • Author(s): 松井太郎、濱田征宏、桑原基、森瀬譲二、岡昌吾、楠 進
  • Organizer: 第２９回日本神経免疫学会学術集会
• [Presentation] イオンチャネル型グルタミン酸受容体に観察される糖鎖の厳密な発現制御 (2017)
  • Author(s): 岡 昌吾
  • Organizer: ２０１７年度生命科学系学会合同年次大会
  • Invited
• [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] 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