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Modular organization of tight junctions and its roles in epithelial plasticity

Research Project

Project/Area Number 18K06234
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionNational Institute for Physiological Sciences

Principal Investigator

Otani Tetsuhisa  生理学研究所, 生体機能調節研究領域, 助教 (50415105)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords密着結合 / 上皮バリア / 上皮極性 / Claudin / JAM / 集団的細胞移動 / 細胞間接着 / メカノバイオロジー / Claudin / JAM / 傍細胞輸送 / 上皮可塑性
Outline of Final Research Achievements

Tight junctions play critical roles in establishing epithelial barrier and polarity. The molecular constituents of tight junctions have been identified. However, how these molecules cooperate to establish epithelial barrier and polarity is not completely understood. In this project, we generated claudin/JAM-A KO cells. Our results revealed that claudins and JAM-A coordinately regulate tight junction formation, epithelial barrier, and polarity. We also found that claudins and JAM-A are required for the collective migration of epithelial sheets during wound healing. These results demonstrate that tight junctions are important for the establishment and maintenance of epithelia.

Academic Significance and Societal Importance of the Research Achievements

上皮組織は外環境と体内を隔てるバリアを構築する。上皮バリアの破綻は炎症性疾患などに伴って認められる。本研究では上皮バリアがClaudinの作る低分子に対するバリアとJAMの作る高分子に対するバリアの二重のバリアから成り立っていることを解明すると共に、ClaudinとJAM-Aが協調的に上皮極性を制御することを明らかにした。本研究の成果を土台として上皮バリアの異常を伴う様々な疾患の理解も進展すると期待される。また、本研究では密着結合が上皮組織の集団的移動にも寄与することを見出し、今後の研究により密着結合の役割の理解が進展することが期待される。

Report

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

    (21 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Int'l Joint Research] University of Munster(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Munster(ドイツ)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Occludin and tricellulin facilitate formation of anastomosing tight-junction strand network to improve barrier function2021

    • Author(s)
      Saito Akira C.、Higashi Tomohito、Fukazawa Yugo、Otani Tetsuhisa、Tauchi Masashi、Higashi Atsuko Y.、Furuse Mikio、Chiba Hideki
    • Journal Title

      Molecular Biology of the Cell

      Volume: 32 Issue: 8 Pages: 722-738

    • DOI

      10.1091/mbc.e20-07-0464

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] New perspective of the structure and function of tight junctions2020

    • Author(s)
      大谷 哲久,古瀬 幹夫
    • Journal Title

      生化学

      Volume: 92 Issue: 5 Pages: 731-734

    • DOI

      10.14952/SEIKAGAKU.2020.920731

    • NAID

      40022394517

    • ISSN
      0037-1017
    • Year and Date
      2020-10-25
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Physiological functions of junctional adhesion molecules (JAMs) in tight junctions2020

    • Author(s)
      Hartmann Christian、Schwietzer Ysabel Alessa、Otani Tetsuhisa、Furuse Mikio、Ebnet Klaus
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Biomembranes

      Volume: 1862 Issue: 9 Pages: 183299-183299

    • DOI

      10.1016/j.bbamem.2020.183299

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tight Junction Structure and Function Revisited2020

    • Author(s)
      Otani Tetsuhisa、Furuse Mikio
    • Journal Title

      Trends in Cell Biology

      Volume: 30 Issue: 10 Pages: 805-817

    • DOI

      10.1016/j.tcb.2020.08.004

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angulin-1 seals tricellular contacts independently of tricellulin and claudins2020

    • Author(s)
      Taichi Sugawara, Kyoko Furuse, Tetsuhisa Otani, Mikio Furuse
    • Journal Title

      bioRxiv

      Volume: - Pages: 323378-323378

    • DOI

      10.1101/2020.10.02.323378

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] The extracellular domain of angulin-1 and palmitoylation of its cytoplasmic region are required for angulin-1 assembly at tricellular contacts2020

    • Author(s)
      Yukako Oda, Taichi Sugawara, Yuko Fukata, Yasushi Izumi, Tetsuhisa Otani, Tomohito Higashi, Masaki Fukata, Mikio Furuse
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 13 Pages: 4289-4302

    • DOI

      10.1074/jbc.ra119.010491

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity2019

    • Author(s)
      Tetsuhisa Otani, Thanh Phuong Nguyen, Shinsaku Tokuda, Kei Sugihara, Taichi Sugawara, Kyoko Furuse, Takashi Miura, Klaus Ebnet, Mikio Furuse
    • Journal Title

      Journal of Cell Biology

      Volume: 218 Issue: 10 Pages: 3372-3396

    • DOI

      10.1083/jcb.201812157

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The plus‐tip tracking and microtubule stabilizing activities of Javelin‐like regulate microtubule organization and cell polarity2019

    • Author(s)
      Raju Baskar, Anna Bahkrat, Tetsuhisa Otani, Housei Wada, Geula Davidov, Himanshu Pandey, Larisa Gheber, Raz Zarivach, Shigeo Hayashi, Uri Abdu
    • Journal Title

      The FEBS journal

      Volume: 286 Issue: 19 Pages: 3811-3830

    • DOI

      10.1111/febs.14944

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effective physical properties of cell-cell interaction explain basic structural units of three-dimensional morphogenesis2019

    • Author(s)
      Hiroshi Koyama, Hisashi Okumura, Atsushi M Ito, Tetsuhisa Otani, Kazuyuki Nakamura, Kagayaki Kato, Toshihiko Fujimori
    • Journal Title

      bioRxiv

      Volume: - Pages: 812198-812198

    • DOI

      10.1101/812198

    • Related Report
      2019 Research-status Report
    • Open Access
  • [Presentation] Quest for claudin-independent occluding junctions in vivo2020

    • Author(s)
      Tetsuhisa Otani
    • Organizer
      53rd Annual meeting of the Japanese Society of Developmental Biologists
    • Related Report
      2020 Annual Research Report
  • [Presentation] Molecular organization of the macromolecule permeability barrier2020

    • Author(s)
      Tetsuhisa Otani, Phuong Nguyen Thanh, Taichi Sugawara, Mikio Furuse
    • Organizer
      The 72nd Annual Meeting of the Japanese Society for Cell Biology
    • Related Report
      2020 Annual Research Report
  • [Presentation] Tight Junction Structure and Function Revisited2020

    • Author(s)
      Tetsuhisa Otani, Thanh Phuong Nguyen, Mikio Furuse
    • Organizer
      MBSJ2020
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Epithelial barrier homeostasis by cell competition.2019

    • Author(s)
      Tetsuhisa Otani and Mikio Furuse
    • Organizer
      52nd Annual meeting of the Japanese Society of Developmental Biologists
    • Related Report
      2019 Research-status Report
  • [Presentation] Genetic dissection of the structural and functional organization of tight junctions.2019

    • Author(s)
      Tetsuhisa Otani, Thanh Phuong Nguyen, and Mikio Furuse
    • Organizer
      Gordon Research Conference on Cell Contact and Adhesion
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genetic dissection of tight junctions.2019

    • Author(s)
      Tetsuhisa Otani, Thanh Phuong Nguyen, and Mikio Furuse
    • Organizer
      Joint Annual Meeting of 71st JSCB and 195h PSSJ
    • Related Report
      2019 Research-status Report
  • [Presentation] ZO family proteins regulate epithelial polarity independent of tight junction strand assembly.2019

    • Author(s)
      Tetsuhisa Otani, Shinsaku Tokuda, Mikio Furuse
    • Organizer
      9th FAOPS Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ZO family proteins regulate epithelial polarity independent of tight junction strand assembly.2018

    • Author(s)
      大谷哲久、徳田深作、古瀬幹夫
    • Organizer
      第70回日本細胞生物学会・第51回日本発生生物学会合同大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 上皮バリアと上皮極性形成における密着結合の役割2018

    • Author(s)
      大谷哲久、徳田深作、古瀬幹夫
    • Organizer
      第8回 生理研・名大医合同シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] ZO family proteins regulate epithelial polarity independent of tight junction strand assembly.2018

    • Author(s)
      Tetsuhisa Otani, Shinsaku Tokuda, Mikio Furuse
    • Organizer
      ASCB/EMBO 2018 meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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

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