Analysis of ER-associated degradation components by multiple knockout cell lines using TALEN

• Project/Area Number: 26840065
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Kyoto University (2015); Okazaki Research Facilities, National Institutes of Natural Sciences (2014)
• Principal Investigator: Ninagawa Satoshi 京都大学, 理学(系)研究科(研究院), 研究員 (80647991)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: EDEM / mannose / N-glycan / 小胞体関連分解 / mannose trimming / 糖鎖 / ERAD / 小胞体 / マンノーストリミング

Outline of Final Research Achievements

Glycoproteins misfolded in the endoplasmic reticulum (ER) are subjected to ER-associated glycoprotein degradation. In this process, N-glycan mannose trimming is required. We clearly showed that this process is initiated by EDEM2 and completed by EDEM3/EDEM1.
We also demonstrated that higher eukaryotes are able to extract severely misfolded glycoproteins from glycoprotein ERAD and target them to the non-glycoprotein ERAD pathway to maintain the homeostasis of the ER.

Research Products

• [Journal Article] Forcible destruction of severely misfolded mammalian glycoproteins by the non-glycoprotein ERAD pathway. (2015)
  • Author(s): Ninagawa S, Okada T, Sumitomo Y, Horimoto S, Sugimoto T, Ishikawa T, Takeda S, Yamamoto T, Suzuki T, Kamiya Y, Kato K, Mori K.
  • Journal Title: The Journal of Cellular Biology Volume: 211 Issue: 4 Pages: 775-784
  • DOI: 10.1083/jcb.201504109
  • NAID: 120005672576
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 糖鎖依存的構造異常タンパク質分解に必須な糖鎖刈り込み機構を解明 革新的ゲノム編集技術によって従来のモデルを一新 (2015)
  • Author(s): 蜷川 暁、加藤 晃一、森 和俊
  • Journal Title: 化学と生物 Volume: Vol.53, No.9 Pages: 571-573
  • NAID: 130005405061
  • Peer Reviewed
• [Journal Article] EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step. (2014)
  • Author(s): Ninagawa S, Okada T, Sumitomo Y, Kamiya Y, Kato K, Horimoto S, Ishikawa T, Takeda S, Sakuma T, Yamamoto T, Mori K
  • Journal Title: J Cell Biol. Volume: 206 Issue: 3 Pages: 347-356
  • DOI: 10.1083/jcb.201404075
  • NAID: 120005468381
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] EDEM1/2/3 are α1,2-mannosidases essential for endoplasmic reticulum-associated degradation of glycoproteins (2014)
  • Author(s): Satoshi Ninagawa, Tetsuya Okada, Yoshiki Sumitomo, Yukiko Kamiya, Satoshi Horimoto, Tokiro Ishikawa, Shunichi Takeda, Tetsushi Sakuma, Takashi Yamamoto, Koichi Kato, Kazutoshi Mori
  • Organizer: SFG JSCR Joint Meeting
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2014-11-16 – 2014-11-19
• [Presentation] 小胞体で新生タンパク質に付加されたN型糖鎖からのマンノーストリミングはEDEM2によって開始される (2014)
  • Author(s): 蜷川暁、岡田徹也、住友嘉樹、神谷由紀子、堀本賢、石川時郎、武田俊一、佐久間 哲史、山本卓、加藤晃一、森和俊
  • Organizer: 第33回日本糖質学会
  • Place of Presentation: 愛知県名古屋市 名古屋大学
  • Year and Date: 2014-08-10 – 2014-08-12