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Integrated understanding of fundamental processes underlying formation of the endoplasmic reticulum network

Research Project

Project/Area Number 16K15218
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionKobe University

Principal Investigator

SAKISAKA Toshiaki  神戸大学, 医学研究科, 教授 (80359843)

Co-Investigator(Kenkyū-buntansha) 山本 泰憲  神戸大学, 医学研究科, 准教授 (30467659)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords細胞小器官 / 小胞体 / 膜変形タンパク質 / 細胞・組織 / 脂質
Outline of Final Research Achievements

Endoplasmic reticulum (ER) is a membrane-bound compartment composed of tubules and sheets in the cytoplasm. The ER tubules connect each other by three-way junctions, resulting in formation of the reticular ER network. While stability of the three-way junctions underlies dynamics of the reticular ER network, the molecular mechanism of how stability of the three-way junctions is regulated remains unclear.
In this study, we revealed that p120, a protein that bound to lunapark, negatively regulated the auto-ubiquitination and proteasomal degradation of lunapark, leading to stabilization of the three-way junctions. Moreover, we identified p57 as a novel ER membrane protein that localized to and regulated the three-way junctions.

Academic Significance and Societal Importance of the Research Achievements

本研究のp120によるlunaparkの自己ユビキチン化を介した分解制御は、小胞体ネットワークの流動性に膜変形タンパク質の分解が大きな寄与をしていることを提示したものであり、学術的な意義が大きいと考えている。また、新規three-way junction局在分子p57の発見は、three-way junctionの動態制御の全容を理解する上で重要な知見である。小胞体ネットワークの破綻は遺伝性痙性対麻痺などの神経変性疾患を引き起こすことから、本研究の成果が神経変性疾患の発症機序の理解や治療薬の開発に繋がる可能性が考えられ、社会的にも意義が大きいと考えている。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2018 2017 2016 Other

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (6 results) Remarks (2 results)

  • [Journal Article] The peroxisome biogenesis factors posttranslationally target reticulon homology domain-containing proteins to the endoplasmic reticulum membrane.2018

    • Author(s)
      Yamamoto, Y. and Sakisaka, T.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 2322-2322

    • DOI

      10.1038/s41598-018-20797-0

    • NAID

      120006728099

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The number of the C-terminal transmembrane domains has the potency to specify subcellular localization of Sec22c.2017

    • Author(s)
      Yamamoto, Y., Yurugi, C., and Sakisaka, T.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 487 Issue: 2 Pages: 388-395

    • DOI

      10.1016/j.bbrc.2017.04.071

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Kif14 overexpression accelerates murine retinoblastoma development.2016

    • Author(s)
      O'Hare, M., Shadmand, M., Sulaiman, R.S., Sishtla, K., Sakisaka, T., and Corson, T.W.
    • Journal Title

      Int. J. Cancer.

      Volume: 139巻8号 Issue: 8 Pages: 1752-1758

    • DOI

      10.1002/ijc.30221

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 小胞体の網目構造を調節する因子の多量体化機構2018

    • Author(s)
      梶保 博昭、山本 泰憲、姜 山、匂坂 敏朗
    • Organizer
      第65回日本生化学会 近畿支部例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ペルオキシソーム形成因子による小胞体膜変形タンパ ク質reticulonの翻訳後膜挿入機構2017

    • Author(s)
      山本泰憲,匂坂敏朗
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] ユビキチンリガーゼ活性による小胞体の新しい形態調 節機構2017

    • Author(s)
      梶保博昭,山本泰憲, 匂坂敏朗
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] 小胞輸送調節タンパク質Sec22CはC末膜貫通領域の数により細胞内局在を制御する2017

    • Author(s)
      山本泰憲,萬木千聖,匂坂敏朗
    • Organizer
      第64回 日本生化学会 近畿支部例会
    • Related Report
      2017 Research-status Report
  • [Presentation] 小胞体膜タンパク質による極長鎖脂肪酸合成の制御2017

    • Author(s)
      内田安則,山本泰憲, 出来宏晃, 匂坂敏朗
    • Organizer
      第64回 日本生化学会 近畿支部例会
    • Related Report
      2017 Research-status Report
  • [Presentation] ユビキチンリガーゼによる小胞体の形態制御機構2017

    • Author(s)
      梶保博昭,姜 山、山本泰憲, 匂坂敏朗
    • Organizer
      第64回 日本生化学会 近畿支部例会
    • Related Report
      2017 Research-status Report
  • [Remarks] 神戸大学医学研究科 生理学・細胞生物学講座 膜動態学ホームページ

    • URL

      http://www.med.kobe-u.ac.jp/membrd/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 膜動態学研究室ホームページ

    • URL

      http://www.med.kobe-u.ac.jp/membrd/

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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