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A study of a calcium-binding protein-regulated network in collagen secretion

Research Project

Project/Area Number 18H02135
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 38030:Applied biochemistry-related
Research InstitutionNagoya University

Principal Investigator

Shibata Hideki  名古屋大学, 生命農学研究科, 准教授 (30314470)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywordsカルシウム / コラーゲン / COPII / 分泌経路 / 小胞体 / COPII小胞
Outline of Final Research Achievements

Collagens are structural proteins that constitute approximately 25% of human dry body weight and are secreted from the endoplasmic reticulum to the extracellular space via the Golgi apparatus. In this study, we aimed to elucidate the molecular mechanisms by which calcium-responsive regulators, mainly the calcium-binding protein ALG-2, control export of collagens from the endoplasmic reticulum, by searching for target molecules of ALG-2 by its binding motifs and by using proximity-dependent labeling methods coupled with mass spectrometry. The protein-protein interaction networks and subcellular localization of multiple candidate regulators and their functions were elucidated by biochemical and molecular cell biological approaches.

Academic Significance and Societal Importance of the Research Achievements

分泌蛋白質のほとんどは、小胞体で合成されゴルジ体を経由して細胞外に分泌される。細胞外マトリクスの主要成分である線維性コラーゲンは、その長さが300 nmにもおよび、小胞体からどのように搬出され細胞外まで輸送されるのか不明であった。近年、線維性コラーゲン輸送の制御因子の同定がすすめられ、その中でALG-2はカルシウムに応答する因子である。本研究では、ALG-2の新たな標的蛋白質を同定し、小胞体内腔のカルシウム濃度の恒常性維持に関わる可能性を示した。また、小胞体からの搬出の制御蛋白質候補も新たに同定されており、線維症などコラーゲン分泌の異常が関連する疾患の新奇の創薬標的になることも期待される。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (13 results)

All 2021 2020 2019 2018 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (4 results) Remarks (2 results)

  • [Journal Article] Amino Acid-Mediated Intracellular Ca2+ Rise Modulates mTORC1 by Regulating the TSC2-Rheb Axis through Ca2+/Calmodulin2021

    • Author(s)
      Amemiya Yuna、Nakamura Nao、Ikeda Nao、Sugiyama Risa、Ishii Chiaki、Maki Masatoshi、Shibata Hideki、Takahara Terunao
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 13 Pages: 6897-6897

    • DOI

      10.3390/ijms22136897

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Novel ALG-2 Target Protein CDIP1 Promotes Cell Death by Interacting with ESCRT-I and VAPA/B2021

    • Author(s)
      Inukai Ryuta、Mori Kanako、Kuwata Keiko、Suzuki Chihiro、Maki Masatoshi、Takahara Terunao、Shibata Hideki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 3 Pages: 1175-1175

    • DOI

      10.3390/ijms22031175

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Penta-EF-Hand ALG-2 Protein Interacts with the Cytosolic Domain of the SOCE Regulator SARAF and Interferes with Ubiquitination2020

    • Author(s)
      Zhang Wei、Muramatsu Ayaka、Matsuo Rina、Teranishi Naoki、Kahara Yui、Takahara Terunao、Shibata Hideki、Maki Masatoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 17 Pages: 6315-6315

    • DOI

      10.3390/ijms21176315

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adaptor functions of the Ca2+-binding protein ALG-2 in protein transport from the endoplasmic reticulum.2019

    • Author(s)
      Shibata H
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 83 Issue: 1 Pages: 20-32

    • DOI

      10.1080/09168451.2018.1525274

    • NAID

      120006718408

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High Sensitive Quantitative Binding Assays Using a Nanoluciferase-Fused Probe for Analysis of ALG-2-Interacting Proteins.2019

    • Author(s)
      Zhang W, Matsuo R, Takahara T, Shibata H, Maki M
    • Journal Title

      Methods Mol Biol

      Volume: 1929 Pages: 501-516

    • DOI

      10.1007/978-1-4939-9030-6_31

    • ISBN
      9781493990290, 9781493990306
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellular Ca2+-Responding Nanoluciferase Reporter Gene System Directed by Tandemly Repeated Pseudo-Palindromic NFAT-Response Elements.2019

    • Author(s)
      Zhang W, Takahara T, Achiha T, Shibata H, Maki M.
    • Journal Title

      Methods Mol Biol

      Volume: 1929 Pages: 95-109

    • DOI

      10.1007/978-1-4939-9030-6_7

    • ISBN
      9781493990290, 9781493990306
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 小胞体からの分子輸送におけるALG-2の役割2018

    • Author(s)
      柴田秀樹、高原照直、京卓志、牧正敏
    • Journal Title

      月刊「細胞」

      Volume: 50 Pages: 441-445

    • Related Report
      2018 Annual Research Report
  • [Presentation] 近接依存性標識法を用いた初期分泌経路制御タンパク質の探索2020

    • Author(s)
      伊藤駿、松下明理、桑田啓子、鄭光傑、高原照直、柴田秀樹
    • Organizer
      第72回日本細胞生物学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ストア作動性カルシウム流入制御因子SARAFの二量体形成におけるALG-2の役割2020

    • Author(s)
      河原由衣、高原照直、柴田秀樹、牧正敏
    • Organizer
      第187回日本農芸化学会中部支部例会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 近接依存性標識法を用いた小胞体の輸送小胞出芽部位に局在するタンパク質の網羅的探索2019

    • Author(s)
      松下明理、高原照直、桑田啓子、牧正敏、柴田秀樹
    • Organizer
      日本農芸化学会 関西・中部支部 2019年度合同神戸大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 近接ラベリング手法を用いたコラーゲン分泌制御因子の網羅的探索2018

    • Author(s)
      松下明理,柴田秀樹,桑田啓子, 高原照直,牧正敏
    • Organizer
      日本農芸化学会中部支部例会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 名古屋大学大学院生命農学研究科分子細胞制御学研究室ホームページ

    • URL

      https://molcellreg.wixsite.com/website

    • Related Report
      2020 Annual Research Report
  • [Remarks] 名古屋大学大学院生命農学研究科分子細胞制御学研究室ホームページ

    • URL

      https://www.agr.nagoya-u.ac.jp/~mcr/

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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