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Elucidation of ERp44-mediated protein quality control system and its physiological significance in the early secretory pathway

Research Project

Project/Area Number 17K15085
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionTohoku University

Principal Investigator

Amagai Yuta  東北大学, 多元物質科学研究所, 助教 (90773896)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsタンパク質品質管理 / ゴルジ体 / 小胞体 / 亜鉛 / ERp44 / シグナル伝達 / 蛋白質 / 細胞・組織
Outline of Final Research Achievements

ERp44 captures ER-resident proteins and immature secretory proteins in the Golgi and transports them back to the ER. In this way, ERp44 contributes to the protein quality control systems in the early secretory pathway. However, the biological significance of ERp44 is not fully understood. In this research, we identified ERp44-binding proteins by BioID2 method and found that ERp44 may participate in the production of extracellular matrix proteins. Furthermore, a series of knockdown experiments showed that zinc transporters regulate ERp44 in cells.

Academic Significance and Societal Importance of the Research Achievements

小胞体-ゴルジ体内腔におけるタンパク質品質管理機構の破綻は、神経変性疾患の原因となることが知られており、その分子基盤の解明は重要である。また、亜鉛は必須微量元素の一つであり、亜鉛の欠損は様々な病態に関連することが知られているが、細胞中での働きについては、あまり理解されていなかった。本研究では、ERp44の生理機能および制御機構を解析することで、亜鉛が分泌経路におけるタンパク質品質管理に関わるという新たな生理機能が解明された。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (8 results)

All 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] IRCCS Ospedale San Raffaele(イタリア)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Zinc regulates ERp44-dependent protein quality control in the early secretory pathway2019

    • Author(s)
      Watanabe Satoshi、Amagai Yuta、Sannino Sara、Tempio Tiziana、Anelli Tiziana、Harayama Manami、Masui Shoji、Sorrentino Ilaria、Yamada Momo、Sitia Roberto、Inaba Kenji
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1-16

    • DOI

      10.1038/s41467-019-08429-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Zinc ions control the function of ERp44 for protein quality control in the early secretory pathway2018

    • Author(s)
      Yuta Amagai, Satoshi Watanabe, Sara Sannino, Momo Yamada, Tiziana Tempio, Manami Harayama, Roberto Sitia and Kenji Inaba
    • Organizer
      International Meeting “Proteins: from the cradle to the grave”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ERp44の機能制御に関わる亜鉛トランスポーターの同定2018

    • Author(s)
      山田 桃、天貝佑太、渡部 聡、Roberto Sitia、稲葉 謙次
    • Organizer
      第41回分子日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 初期分泌経路内のタンパク質品質管理におけるERp44の新たな生理的機能の探索2018

    • Author(s)
      天貝佑太、稲葉謙次
    • Organizer
      第41回分子日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Zn2+ controls the function of ERp44 in the early secretory pathway2018

    • Author(s)
      Yuta Amagai, Satoshi Watanabe, Sara Sannino, Manami Harayama, Shoji Masui, Tiziana Tempio, Momo Yamada, Ilaria Sorrentino, Tiziana Anelli, Roberto Sitia, Kenji Inaba
    • Organizer
      CLS, Tokyo Tech. International Forum 2018, Redox regulation of protein functions, transcription, translation and folding
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 亜鉛イオンとの結合を介したERp44による分泌経路中のタンパク質品質管理機構2017

    • Author(s)
      天貝佑太、渡部聡、原山麻奈美、増井翔史、Sara Sannino、Roberto Sitia、稲葉謙次
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 亜鉛イオンはERp44によるタンパク質品質管理機構を制御する2017

    • Author(s)
      天貝佑太、渡部聡、原山麻奈美、山田桃、Sara Sannino、Roberto Sitia、稲葉謙次
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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