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Molecular understanding of osmotic stress sensing and response

Research Project

Project/Area Number 18H03995
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

ICHIJO HIDENORI  東京大学, 大学院薬学系研究科(薬学部), 教授 (00242206)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥44,460,000 (Direct Cost: ¥34,200,000、Indirect Cost: ¥10,260,000)
Fiscal Year 2020: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2019: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
Fiscal Year 2018: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
KeywordsASK3 / 浸透圧ストレス受容 / 浸透圧ストレス応答 / 細胞体積制御 / VRAC/LRRC8 / アポトーシス / 液―液相分離 / ポリADPリボース / 浸透圧受容 / 浸透圧応答 / 細胞体積
Outline of Final Research Achievements

Cells are constantly exposed to osmotic stress that forces them to change their volume due to osmotic pressure differences between the inside and outside of the cell, so called osmotic stress, and they maintain a constant volume by sensing osmotic pressure changes and responding appropriately. Until now, most studies have been based on the idea that osmotic changes without physical substance are sensed through changes in the cell membrane, which is in contact with the extracellular environment.
Using the ASK3 protein as a research model, we have elucidated that cells sense osmotic stress internally using the physical phenomenon of liquid-liquid phase separation as a "trigger". These are the results of taking advantage of molecular biological and biochemical methods and computer simulations.

Academic Significance and Societal Importance of the Research Achievements

本研究はいわゆる基礎研究に相当しますが、本研究成果によってASK3の役割から期待される高血圧疾患や浮腫などに対する新規治療薬の開発に向けて前進しました。さらに本研究成果によって得られた知見を活かして液―液相分離を積極的に操作することで、神経変性疾患など多くの疾患に対する新規治療戦略の開発に発展することも期待されます。

Report

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

    (42 results)

All 2021 2020 2019 2018 2017

All Journal Article (25 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 25 results,  Open Access: 20 results) Presentation (17 results) (of which Invited: 1 results)

  • [Journal Article] Cells recognize osmotic stress through liquid-liquid phase separation lubricated with poly(ADP-ribose)2021

    • Author(s)
      Watanabe Kengo、Morishita Kazuhiro、Zhou Xiangyu、Shiizaki Shigeru、Uchiyama Yasuo、Koike Masato、Naguro Isao、Ichijo Hidenori
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 1353-1353

    • DOI

      10.1038/s41467-021-21614-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Lens for Cell Volume Regulation: Liquid-Liquid Phase Separation2021

    • Author(s)
      Ishihara, S., Ichijo, H., Watanabe, K.
    • Journal Title

      Cellular Physiology and Biochemistry

      Volume: 55 Issue: S1 Pages: 135-160

    • DOI

      10.33594/000000357

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The mitochondrial Ca2+ uptake regulator, MICU1, is involved in cold stress‐induced ferroptosis2021

    • Author(s)
      Nakamura Toshitaka、Ogawa Motoyuki、Kojima Kazuki、Takayanagi Saki、Ishihara Shunya、Hattori Kazuki、Naguro Isao、Ichijo Hidenori
    • Journal Title

      EMBO reports

      Volume: 22 Issue: 5

    • DOI

      10.15252/embr.202051532

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ASK1 suppresses NK cell-mediated intravascular tumor cell clearance in lung metastasis.2021

    • Author(s)
      Fujimoto, M., Kamiyama, M., Fuse, K., Ryuno, H., Odawara, T., Furukawa, N., Yoshimatsu, Y., Watabe, T., Michaela, P.-M., Veronika, S., Tahara, H., Hayakawa, Y., Sato, T., Takeda, K., Naguro, I. and Ichijo, H.
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 4 Pages: 1633-1643

    • DOI

      10.1111/cas.14842

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] FGF21 Induced by the ASK1-p38 Pathway Promotes Mechanical Cell Competition by Attracting Cells2021

    • Author(s)
      Ogawa Motoyuki、Kawarazaki Yosuke、Fujita Yasuyuki、Naguro Isao、Ichijo Hidenori
    • Journal Title

      Current Biology

      Volume: 31 Issue: 5 Pages: 1048-1057

    • DOI

      10.1016/j.cub.2020.11.052

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular functions of ASK family in diseases caused by stress-induced inflammation and apoptosis2020

    • Author(s)
      Kojima Kazuki、Ichijo Hidenori、Naguro Isao
    • Journal Title

      The Journal of Biochemistry

      Volume: in press Issue: 4 Pages: 395-407

    • DOI

      10.1093/jb/mvaa145

    • NAID

      40022588047

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The CCR4-NOT deadenylase complex safeguards thymic positive selection by down-regulating aberrant pro-apoptotic gene expression2020

    • Author(s)
      Ito-Kureha Taku、Miyao Takahisa、Nishijima Saori、Suzuki Toru、Koizumi Shin-ichi、Villar-Briones Alejandro、Takahashi Akinori、Akiyama Nobuko、Morita Masahiro、Naguro Isao、Ishikawa Hiroki、Ichijo Hidenori、Akiyama Taishin、Yamamoto Tadashi
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 6169-6169

    • DOI

      10.1038/s41467-020-19975-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] β-adrenergic receptor signaling evokes the PKA-ASK axis in mature brown adipocytes2020

    • Author(s)
      Hattori Kazuki、Wakatsuki Hiroaki、Sakauchi Chihiro、Furutani Shotaro、Sugawara Sho、Hatta Tomohisa、Natsume Tohru、Ichijo Hidenori
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 10 Pages: e0232645-e0232645

    • DOI

      10.1371/journal.pone.0232645

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Apoptosis signal-regulating kinase 1 (ASK1) as a therapeutic target for neurological diseases2020

    • Author(s)
      Takenaka Satoshi、Fujisawa Takao、Ichijo Hidenori
    • Journal Title

      Expert Opinion on Therapeutic Targets

      Volume: 24 Issue: 11 Pages: 1061-1064

    • DOI

      10.1080/14728222.2020.1821648

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform identifies features important for substrate permeation2020

    • Author(s)
      Nakamura Ryoki、Numata Tomohiro、Kasuya Go、Yokoyama Takeshi、Nishizawa Tomohiro、Kusakizako Tsukasa、Kato Takafumi、Hagino Tatsuya、Dohmae Naoshi、Inoue Masato、Watanabe Kengo、Ichijo Hidenori、Kikkawa Masahide、Shirouzu Mikako、Jentsch Thomas J.、Ishitani Ryuichiro、Okada Yasunobu、Nureki Osamu
    • Journal Title

      Communications Biology

      Volume: 3 Issue: 1 Pages: 240-240

    • DOI

      10.1038/s42003-020-0951-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The mitochondrial protein PGAM5 suppresses energy consumption in brown adipocytes by repressing expression of uncoupling protein 1.2020

    • Author(s)
      Sugawara, S., Kanamaru, Y., Sekine, S., Maekawa, L., Takahashi, A., Yamamoto, T., Watanabe, K., Fujisawa, T., Hattori, K. and Ichijo, H.
    • Journal Title

      J. Biol. Chem.

      Volume: 295 Issue: 17 Pages: 5588-5601

    • DOI

      10.1074/jbc.ra119.011508

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ASK1 promotes uterine inflammation leading to pathological preterm birth2020

    • Author(s)
      Yoshikawa Midori、Iriyama Takayuki、Suzuki Kensuke、Sayama Seisuke、Tsuruga Tetsushi、Kumasawa Keiichi、Nagamatsu Takeshi、Homma Kengo、Naguro Isao、Osuga Yutaka、Ichijo Hidenori、Fujii Tomoyuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 1887-1887

    • DOI

      10.1038/s41598-020-58653-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue.2020

    • Author(s)
      Kato H, Okabe K, Miyake M, Hattori K, Fukaya T, Tanimoto K, Beini S, Mizuguchi M, Torii S, Arakawa S, Ono M, Saito Y, Sugiyama T, Funatsu T, Sato K, Shimizu S, Oyadomari S, Ichijo H, Kadowaki H, Nishitoh H.
    • Journal Title

      Life science alliance

      Volume: 3 Issue: 3 Pages: 201900576-201900576

    • DOI

      10.26508/lsa.201900576

    • NAID

      120006980545

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide siRNA screening reveals that DCAF4-mediated ubiquitination of optineurin stimulates autophagic degradation of Cu/Zn superoxide dismutase.2020

    • Author(s)
      Homma, K., Takahashi, H., Tsuburaya, N., Naguro, I., Fujisawa, T. and Ichijo, H.
    • Journal Title

      J. Biol. Chem.

      Volume: 295 Issue: 10 Pages: 3148-3158

    • DOI

      10.1074/jbc.ra119.010239

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Iron homeostasis and iron-regulated ROS in cell death, senescence and human diseases.2019

    • Author(s)
      Nakamura, T., Naguro, I. and Ichijo, H.
    • Journal Title

      Biochim. Biophys. Acta. Gen. Subj.

      Volume: pii Issue: 9 Pages: 1398-1409

    • DOI

      10.1016/j.bbagen.2019.06.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell volume regulation in cancer cell migration driven by osmotic water flow2019

    • Author(s)
      Morishita Kazuhiro、Watanabe Kengo、Ichijo Hidenori
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 8 Pages: 2337-2347

    • DOI

      10.1111/cas.14079

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] β-TrCP-dependent degradation of ASK1 suppresses the induction of the apoptotic response by oxidative stress2018

    • Author(s)
      Cheng Ran、Takeda Kohsuke、Naguro Isao、Hatta Tomohisa、Iemura Shun-ichiro、Natsume Tohru、Ichijo Hidenori、Hattori Kazuki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1862 Issue: 10 Pages: 2271-2280

    • DOI

      10.1016/j.bbagen.2018.07.015

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A small-molecule inhibitor of SOD1-Derlin-1 interaction ameliorates pathology in an ALS mouse model2018

    • Author(s)
      Tsuburaya, N., Homma, K., Higuchi, T., Balia, A., Yamakoshi, H., Shibata, N., Nakamura, S., Nakagawa, H., Ikeda, S., Umezawa, N., Kato, N., Yokoshima, S., Shibuya, M., Shimonishi, M., Kojima, H., Okabe, T., Nagano, T., Naguro, I., Imamura, K., Inoue, H., Fujisawa, T., and Ichijo, H.
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 2668-2668

    • DOI

      10.1038/s41467-018-05127-2

    • NAID

      120006546002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cryo-EM structure of the volume-regulated anion channel LRRC82018

    • Author(s)
      Kasuya Go、Nakane Takanori、Yokoyama Takeshi、Jia Yanyan、Inoue Masato、Watanabe Kengo、Nakamura Ryoki、Nishizawa Tomohiro、Kusakizako Tsukasa、Tsutsumi Akihisa、Yanagisawa Haruaki、Dohmae Naoshi、Hattori Motoyuki、Ichijo Hidenori、Yan Zhiqiang、Kikkawa Masahide、Shirouzu Mikako、Ishitani Ryuichiro、Nureki Osamu
    • Journal Title

      Nat. Struct. Mol. Biol.

      Volume: 25 Pages: 797-804

    • DOI

      10.1101/331207

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ASK family kinases mediate cellular stress and redox signaling to circadian clock2018

    • Author(s)
      Imamura Kiyomichi、Yoshitane Hikari、Hattori Kazuki、Yamaguchi Mitsuo、Yoshida Kento、Okubo Takenori、Naguro Isao、Ichijo Hidenori、Fukada Yoshitaka
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 14 Pages: 3646-3651

    • DOI

      10.1073/pnas.1719298115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A PP6-ASK3 Module Coordinates the Bidirectional Cell Volume Regulation under Osmotic Stress2018

    • Author(s)
      Watanabe Kengo、Umeda Tsuyoshi、Niwa Kuniyoshi、Naguro Isao、Ichijo Hidenori
    • Journal Title

      Cell Reports

      Volume: 22 Issue: 11 Pages: 2809-2817

    • DOI

      10.1016/j.celrep.2018.02.045

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.2018

    • Author(s)
      Galluzzi, L. et al.
    • Journal Title

      Cell Death Differ.

      Volume: 25 Issue: 3 Pages: 486-541

    • DOI

      10.1038/s41418-017-0012-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] mASKing cancer cells in a tumor microenvironment2018

    • Author(s)
      Kamiyama Miki、Naguro, Isao、Ichijo Hidenori
    • Journal Title

      Cell Cycle

      Volume: 17 Issue: 2 Pages: 139-140

    • DOI

      10.1080/15384101.2017.1407402

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Apoptosis signal-regulating kinase 1 in regulated necrosis2018

    • Author(s)
      Hattori Kazuki、Ichijo Hidenori
    • Journal Title

      Cell Cycle

      Volume: 17 Issue: 1 Pages: 5-6

    • DOI

      10.1080/15384101.2017.1397330

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of ASK1/p38 Cascade in a Mouse Model of Alzheimer’s Disease and Brain Aging2017

    • Author(s)
      Hasegawa Yu、Toyama Kensuke、Uekawa Ken、Ichijo Hidenori、Kim-Mitsuyama Shokei
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 61 Issue: 1 Pages: 259-263

    • DOI

      10.3233/jad-170645

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] TRPM4は細胞内液滴の流動性制御を介してASK3不活性化に寄与する2020

    • Author(s)
      森下和浩、渡邊謙吾、名黒功、一條秀憲
    • Organizer
      若手ファーマバイオフォーラム2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] 浸透圧ストレス応答と細胞死制御における体積調節の共通性2019

    • Author(s)
      井上雅斗、渡邊謙吾、一條秀憲
    • Organizer
      第28回日本Cell Death学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 相分離が高浸透圧ストレス下でのPP6によるASK3不活性化を制御する2019

    • Author(s)
      渡邊謙吾、名黒功、一條秀憲
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ASK1はNOD-RIPK2経路を抑制し脂肪細胞での炎症応答を制御する2019

    • Author(s)
      高柳早希、渡邊謙吾、一條秀憲
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ASK3不活性化における高浸透圧ストレスセンサー候補分子TRPM4の機能解析2019

    • Author(s)
      森下和浩、渡邊謙吾、一條秀憲
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ポリADPリボースは液-液相分離を介して浸透圧ストレス応答キナーゼASK3を制御する2019

    • Author(s)
      渡邊謙吾、森下和浩、一條秀憲
    • Organizer
      第14回日本臨床ストレス応答学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ASK1はNOD-RIPK2経路を抑制し脂肪細胞での炎症応答を制御する2019

    • Author(s)
      高柳早希、渡邊謙吾、一條秀憲
    • Organizer
      第14回日本臨床ストレス応答学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ASK3不活性化における高浸透圧ストレスセンサー候補分子TRPM4の機能解析2019

    • Author(s)
      森下和浩、渡邊謙吾、一條秀憲
    • Organizer
      第14回日本臨床ストレス応答学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ASK1はNOD-RIPK2経路を抑制し褐色脂肪細胞での炎症応答を制御する2019

    • Author(s)
      高柳早希、渡邊謙吾、一條秀憲
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ASK3不活性化における高浸透圧ストレスセンサー候補分子TRPM4の機能解析2019

    • Author(s)
      森下和浩、渡邊謙吾、石原駿弥、一條秀憲
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ASK3 modulates cell volume under osmotic stress and beyond.2018

    • Author(s)
      渡邊謙吾、一條秀憲
    • Organizer
      第10回シグナルネットワーク研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ストレスシグナルによる神経変性制御2018

    • Author(s)
      一條秀憲
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ASK3による体積調節を介した細胞死制御2018

    • Author(s)
      井上雅斗、渡邊謙吾、一條秀憲
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ASK1はNOD-RIPK2経路を制御する2018

    • Author(s)
      高柳早希、渡邊謙吾、一條秀憲
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] プロテアソーム依存的なASK3の不活性化による高浸透圧ストレス応答の制御2018

    • Author(s)
      周翔宇、渡邊謙吾、森下和浩、名黒功、一條秀憲
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ASK3による体積調節を介した細胞死制御2018

    • Author(s)
      井上雅斗、渡邊謙吾、一條秀憲
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ASK3不活性化における高浸透圧ストレスセンサー候補分子TRPML1の機能解析2018

    • Author(s)
      森下和浩、渡邊謙吾、一條秀憲
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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