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Discovery of ER-endomannosidase and its importance on glycoprotein quality control

Research Project

Project/Area Number 25560420
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Chemical biology
Research InstitutionSeikei University

Principal Investigator

Totani Kiichiro  成蹊大学, 理工学部, 准教授 (80360593)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords糖鎖 / 酵素 / 合成化学 / タンパク質品質管理 / 糖タンパク質品質管理 / 阻害剤 / 基質 / エンドマンノシダーゼ / カルネキシンサイクル / 合成糖鎖プローブ
Outline of Final Research Achievements

We previously have found an endomannosidase (EM) activity in the endoplasmic reticulum (ER). Since ER-EM will play important roles for releasing unfolded glycoproteins from the folding system, calnexin/calreticulin cycle, herein we synthesized inhibitors and substrates contributing functional analysis of this enzyme. To explore the origin of ER-EM activity, we examined blue native PAGE with MS/MS analysis. Moreover, we generated a recombinant enzyme of ER-EM candidate, resulted in the ER-localization of the candidate enzyme was also elucidated. Additionally, specificity analyses of calreticulin and UGGT that are related to functions of ER-EM, were also carried out.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (38 results)

All 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 4 results) Presentation (29 results) (of which Int'l Joint Research: 4 results,  Invited: 5 results) Book (4 results)

  • [Int'l Joint Research] メルボルン大学(オーストラリア)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Calreticulin discriminates the proximal region at the N-glycosylation site of Glc1Man9GlcNAc2 ligand2015

    • Author(s)
      Makoto Hirano, Yuka Adachi, Yukishige Ito, Kiichiro Totani
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 466 Issue: 3 Pages: 350-355

    • DOI

      10.1016/j.bbrc.2015.09.026

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Silyl-assisted 1,2-cis-α-glucosylation for the synthesis of a triglucoside moiety in high-mannose-type oligosaccharides2015

    • Author(s)
      Kiichiro Totani, Yuki Shinoda, Masaaki Shiba, Shogo Iwamoto, Akira Koizumi, Yuji Matsuzaki, Makoto Hirano
    • Journal Title

      RSC Advances

      Volume: 5 Issue: 93 Pages: 75918-75922

    • DOI

      10.1039/c5ra16659d

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Analytical method for determining relative chaperone activity using an ovalbumin-conjugated column2015

    • Author(s)
      Makoto Hirano, Yuki Kato, Ayami Imagawa, Kiichiro Totani
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 456 Issue: 1 Pages: 333-338

    • DOI

      10.1016/j.bbrc.2014.11.081

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Glycopeptide probes for understanding peptide specificity of the folding sensor enzyme UGGT2014

    • Author(s)
      Takaya Kudo, Makoto Hirano, Toshihiro Ishihara, Shun Shimura, Kiichiro Totani
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 24 Issue: 24 Pages: 5563-5567

    • DOI

      10.1016/j.bmcl.2014.11.013

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Two independent pathways on mannose trimmings in the ER glycoprotein quality control2015

    • Author(s)
      Taiki Kuribara, Makoto Hirano, Spencer J. Williams, Yukishige Ito, Kiichiro Totani
    • Organizer
      23rd International Symposium on Glycoconjugates
    • Place of Presentation
      Hotel Le Meridien Lav Sprit, Sprit (Croatia)
    • Year and Date
      2015-09-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biological significance of endomannosidase activity in the endoplasmic reticulum2015

    • Author(s)
      Makoto Hirano, Chie Wtanabe, Yukishige Ito, Spencer J. Williams, Kiichiro Totani
    • Organizer
      23rd International Symposium on Glycoconjugates
    • Place of Presentation
      Hotel Le Meridien Lav Sprit, Sprit (Croatia)
    • Year and Date
      2015-09-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chemical approaches for connecting missing links in discrimination between folded and unfolded glycoprotein in the ER2015

    • Author(s)
      Kiichiro Totani, Makoto Hirano, Yukishige Ito
    • Organizer
      23rd International Symposium on Glycoconjugates
    • Place of Presentation
      Hotel Le Meridien Lav Sprit, Sprit (Croatia)
    • Year and Date
      2015-09-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biological significance of an endomannosidase found in the endoplasmic reticulum: triaging Glc1Man9GlcNAc2-glycoproteins2015

    • Author(s)
      Makoto Hirano, Chie Watanabe, Yukishige Ito, Kiichiro Totani
    • Organizer
      The 4th Joint Austria/Japan Seminar on Comparative and Developmental Glycobiology
    • Place of Presentation
      Hotel Le Meridien Lav Sprit, Sprit (Croatia)
    • Year and Date
      2015-09-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 小胞体エンドマンノシダーゼは糖タンパク質をトリアージする2015

    • Author(s)
      平野真,渡邊千惠,伊藤幸成,Spencer J. Williams,戸谷希一郎
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学安田講堂(東京)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] 小胞体における独立した2つのマンノーストリミング経路2015

    • Author(s)
      栗原大輝,平野真,伊藤幸成,戸谷希一郎
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学安田講堂(東京)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] 糖ペプチドプローブを用いた糖タンパク質折り畳みセンサー酵素 UGGT のペプチド特異性解析2015

    • Author(s)
      戸谷希一郎,工藤貴弥,平野真,石原俊洋,志村俊
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学安田講堂(東京)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] Biological function of endomannosidase activity found in the endoplasmic reticulum2014

    • Author(s)
      Makoto Hirano, Chie Wtanabe, Karen Kubo, Yukishige Ito, Spencer J. Williams, Kiichiro Totani
    • Organizer
      Joint Meeting of the Society for Glycobiology and the Japanese Society of Carbohydrate Research
    • Place of Presentation
      Hilton Hawaiian Village (USA)
    • Year and Date
      2014-11-16 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] Chemical approaches for connecting missing links in glycoprotein quality control2014

    • Author(s)
      Kiichiro Totani
    • Organizer
      Third Japanese-Swiss Chemical Biology Symposium
    • Place of Presentation
      University of Bern, Bern (Swiss)
    • Year and Date
      2014-10-02 – 2014-10-03
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 合成小分子が拓くタンパク質表面における糖鎖機能の分子基盤2014

    • Author(s)
      戸谷希一郎,
    • Organizer
      第65回コロイドおよび界面化学討論会「バイオナノ界面の新潮流」
    • Place of Presentation
      東京理科大学(東京)
    • Year and Date
      2014-09-03
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 小胞体に見出されたエンドマンノシダーゼ活性の解析2014

    • Author(s)
      平野真,渡邊千惠,久保佳蓮,伊藤幸成,Spencer J. Williams,戸谷希一郎
    • Organizer
      第33回日本糖質学会年会
    • Place of Presentation
      名古屋大学豊田講堂(愛知)
    • Year and Date
      2014-08-10 – 2014-08-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 小胞体におけるエンドマンノシダーゼ活性の探索2014

    • Author(s)
      平野真,渡邊千惠,戸谷希一郎
    • Organizer
      第9回日本ケミカルバイオロジー学会年会
    • Place of Presentation
      大阪大学豊中キャンパス(大阪)
    • Year and Date
      2014-06-11 – 2014-06-13
    • Related Report
      2014 Research-status Report
  • [Presentation] カルレティキュリンのアグリコン特異性解析2014

    • Author(s)
      戸谷希一郎
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学・東山キャンパス(愛知)
    • Related Report
      2013 Research-status Report
  • [Presentation] 小胞体エンドマンノシダーゼに対する小分子基質の合成研究2014

    • Author(s)
      齋藤信彦
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学・東山キャンパス(愛知)
    • Related Report
      2013 Research-status Report
  • [Presentation] Chemical approaches toward understanding of ER endomannosidase2013

    • Author(s)
      Kiichiro Totani
    • Organizer
      Third Joint Austria/Japan Seminar on Comparative and Developmental Glycobiology
    • Place of Presentation
      RIKEN, Wako (Japan)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 糖鎖のはたらきを知るための化学的アプローチ2013

    • Author(s)
      戸谷希一郎
    • Organizer
      化学と生命のかけはし
    • Place of Presentation
      東京大学工学部(東京)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 合成基質を用いた小胞体エンドマンノシダーゼの機能解析2013

    • Author(s)
      戸谷希一郎
    • Organizer
      第8回日本ケミカルバイオロジー学会年会
    • Place of Presentation
      東京医科歯科大学M&Dタワー鈴木章夫記念講堂(東京)
    • Related Report
      2013 Research-status Report
  • [Presentation] 小胞体エンドマンノシダーゼの機能解析2013

    • Author(s)
      戸谷希一郎
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      東大阪国際交流センター(大阪)
    • Related Report
      2013 Research-status Report
  • [Presentation] UGGTのアグリコン特異性解析を志向した糖ペプチド型阻害剤の合成研究2013

    • Author(s)
      工藤貴弥
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      東大阪国際交流センター(大阪)
    • Related Report
      2013 Research-status Report
  • [Presentation] 均一糖鎖を持つメガリンの合成研究2013

    • Author(s)
      横溝里佳
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      東大阪国際交流センター(大阪)
    • Related Report
      2013 Research-status Report
  • [Presentation] UGGTの糖鎖特異性解析を志向した非天然N-結合型コア糖鎖の合成研究2013

    • Author(s)
      荒木千広
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      東大阪国際交流センター(大阪)
    • Related Report
      2013 Research-status Report
  • [Presentation] クラゲムチンによる糖加水分解反応の性状解析2013

    • Author(s)
      鈴木綾
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      東大阪国際交流センター(大阪)
    • Related Report
      2013 Research-status Report
  • [Presentation] 糖タンパク質品質管理に関わる糖鎖プロセシングのアグリコン特異性解析2013

    • Author(s)
      山谷健太
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      東大阪国際交流センター(大阪)
    • Related Report
      2013 Research-status Report
  • [Presentation] 安定同位体標識と常磁性プローブ導入による高マンノース型糖鎖のNMR動的構造解析2013

    • Author(s)
      山口拓実
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      東大阪国際交流センター(大阪)
    • Related Report
      2013 Research-status Report
  • [Presentation] UGGTのアグリコン特異性解析を志向した糖ペプチドの合成研究2013

    • Author(s)
      工藤貴弥
    • Organizer
      GlycoTOKYO2013シンポジウム
    • Place of Presentation
      成蹊大学4号館ホール(東京)
    • Related Report
      2013 Research-status Report
  • [Presentation] 小胞体マンノシダーゼ類に対する選択的阻害剤の探索2013

    • Author(s)
      栗原大輝
    • Organizer
      GlycoTOKYO2013シンポジウム
    • Place of Presentation
      成蹊大学4号館ホール(東京)
    • Related Report
      2013 Research-status Report
  • [Presentation] アグリコンの疎水性度に着目したカルレティキュリンとGlc1Man9GlcNAc2誘導体との相互作用解析2013

    • Author(s)
      平野真
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Related Report
      2013 Research-status Report
  • [Presentation] アグリコン構造が小胞体糖鎖プロセシングに与える影響2013

    • Author(s)
      山谷健太
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Related Report
      2013 Research-status Report
  • [Presentation] CNX/CRTサイクル関連タンパク質の階層横断解析2013

    • Author(s)
      今川綾望
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Related Report
      2013 Research-status Report
  • [Book] 糖タンパク質品質管理の稼働状況を知る~化学合成基質による糖鎖プロファイルの再構成~ 糖鎖の新機能開発・応用ハンドブック2015

    • Author(s)
      岩本将吾, 平野真,松尾一郎, 戸谷希一郎
    • Total Pages
      628
    • Publisher
      NTS
    • Related Report
      2015 Annual Research Report
  • [Book] 糖タンパク質品質管理の稼働状況を知る~化学合成基質による糖鎖プロファイルの再構成~, 糖鎖の新機能開発・応用ハンドブック2015

    • Author(s)
      岩本将吾, 松尾一郎, 戸谷希一郎
    • Publisher
      NTS
    • Related Report
      2014 Research-status Report
  • [Book] 糖タンパク質品質管理の稼働状況を知る~化学合成基質による糖鎖プロファイルの再構成~: 糖鎖の新機能開発・応用ハンドブック;2014

    • Author(s)
      戸谷希一郎
    • Publisher
      NTS
    • Related Report
      2013 Research-status Report
  • [Book] 高マンノース型糖鎖の合成とバイオロジーへの展開:第三の生命鎖糖鎖の機能と疾患2013

    • Author(s)
      戸谷希一郎
    • Total Pages
      228
    • Publisher
      羊土社
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2022-02-01  

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