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The mechanism of the tight junction morphology formation

Research Project

Project/Area Number 21H02523
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 44040:Morphology and anatomical structure-related
Research InstitutionNational Institute for Physiological Sciences

Principal Investigator

Furuse Mikio  生理学研究所, 生体機能調節研究領域, 教授 (90281089)

Co-Investigator(Kenkyū-buntansha) 菅原 太一  熊本大学, 大学院先導機構, 助教 (30758412)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2022: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2021: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords上皮細胞 / タイトジャンクション / クローディン / 上皮バリア機能 / 細胞間接着 / JAM / CAR / ZO-1 / 電子顕微鏡 / 微細形態
Outline of Research at the Start

タイトジャンクション(TJ)は、細胞同士の隙間を塞ぐことにより上皮バリア機能に寄与する細胞間結合である。本研究では、TJの機能制御に直結する特徴的な形態である1)局所的に形成されるTJのベルト構造、2)細胞あたりのTJの量の多様性、3)細胞あたりのTJの総延長の多様性を生み出すメカニズムを分子レベルで明らかにする。

Outline of Final Research Achievements

The mechanism of tight junction (TJ) formation was analyzed by re-expressing claudin in TJ-deficient epithelial cells, which were established by deleting five claudin genes from the epithelial cell line MDCK cells. The results revealed that many claudin subtypes can form TJs by themselves, while some cannot; that the charge-selective channels formed by the pore-forming claudin subtypes are formed by the subtype alone and do not require the involvement of other subtypes; and that ZO-1, a scaffold protein interacting with claudins, is not required for positioning of TJ formation. Furthermore, we found that the TJ membrane proteins claudin and JAM-A cooperatively contribute to the homeostasis of the epithelial cell-cell adhesion complex.

Academic Significance and Societal Importance of the Research Achievements

タイトジャンクションが形成する細胞間隙の水溶性分子に対する透過バリアは、腸管バリア、皮膚バリア、血液脳関門といった私達の生存に必須な生体内バリアを形作っている。したがって、タイトジャンクションの形成機構について新しい知見を得た本研究は、きわめて基礎的であるが、基礎医学的に重要であるばかりでなく、タイトジャンクション形成の人為的コントロールにより医学応用を目指す研究にも重要な示唆を与える。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (27 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (4 results) Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Open Access: 7 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Remarks (2 results)

  • [Int'l Joint Research] シャリテー ベルリン医科大学(ドイツ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Leibniz-Forschungsinstitut/Kiel University/Charite(ドイツ)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University College London(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University of Bern(スイス)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Tight junction membrane proteins regulate the mechanical resistance of the apical junctional complex2024

    • Author(s)
      Nguyen Thanh Phuong、Otani Tetsuhisa、Tsutsumi Motosuke、Kinoshita Noriyuki、Fujiwara Sachiko、Nemoto Tomomi、Fujimori Toshihiko、Furuse Mikio
    • Journal Title

      Journal of Cell Biology

      Volume: 223 Issue: 5 Pages: 1-23

    • DOI

      10.1083/jcb.202307104

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reconstitution of functional tight junctions with individual claudin subtypes in epithelial cells2023

    • Author(s)
      Ryutaro Kasikuma, Makoto Nagano, Hiroyuki Shimamura, Kouya Nukaga, Ikumi Katsumata, Junko Y. Toshima, Jiro Toshima
    • Journal Title

      Cell Structure and Function

      Volume: 48 Issue: 1 Pages: 1-17

    • DOI

      10.1247/csf.22068

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanism of interdigitation formation at apical boundary of MDCK cell2023

    • Author(s)
      S Miyazaki, T Otani, K Sugihara, T Fujimori, M Furuse, T Miura
    • Journal Title

      iScience

      Volume: 26 Issue: 5 Pages: 1-21

    • DOI

      10.1016/j.isci.2023.106594

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of the genes encoding candidate septate junction components expressed during early development of the sea urchin, Strongylocentrotus purpuratus, and evidence of a role for Mesh in the formation of the gut barrier2023

    • Author(s)
      Jonusaite Sima、Oulhen Nathalie、Izumi Yasushi、Furuse Mikio、Yamamoto Takashi、Sakamoto Naoaki、Wessel Gary、Heyland Andreas
    • Journal Title

      Developmental Biology

      Volume: 495 Pages: 21-34

    • DOI

      10.1016/j.ydbio.2022.12.007

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] JAM-A interacts with α3β1 integrin and tetraspanins CD151 and CD9 to regulate collective cell migration of polarized epithelial cells2022

    • Author(s)
      Sonja Thölmann, Jochen Seebach, Tetsuhisa Otani, Luise Florin, Hans Schnittler, Volker Gerke, Mikio Furuse, Klaus Ebnet
    • Journal Title

      Cellular and Molecular Life Sciences

      Volume: 79 Issue: 2 Pages: 1-19

    • DOI

      10.1007/s00018-022-04140-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Erebosis, a new cell death mechanism during homeostatic turnover of gut enterocytes2022

    • Author(s)
      Hanna M Ciesielski, Hiroshi Nishida, Tomomi Takano, Aya Fukuhara, Tetsuhisa Otani, Yuko Ikegawa, Morihiro Okada, Takashi Nishimura, Mikio Furuse, Sa Kan Yoo
    • Journal Title

      PLoS Biol.

      Volume: 20 Issue: 4 Pages: e3001586-e3001586

    • DOI

      10.1371/journal.pbio.3001586

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tight junction formation by a claudin mutant lacking the COOH-terminal PDZ domain-binding motif2022

    • Author(s)
      Sachiko Fujiwara, Thanh Phuong Nguyen, Kyoko Furuse, Yugo Fukazawa, Tetsuhisa Otani, Mikio Furuse
    • Journal Title

      Ann N Y Acad Sci.

      Volume: 1516 Issue: 1 Pages: 85-94

    • DOI

      10.1111/nyas.14881

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nanoscale segregation of channel and barrier claudins enables paracellular ion flux.2022

    • Author(s)
      Gonschior H, Schmied C, Eva Van der Veen R, Eichhorst J, Himmerkus N, Piontek J, Gunzel D, Bleich M, Furuse M, Haucke V, Lehmann M.
    • Journal Title

      Nat Commun.

      Volume: 13 Issue: 1 Pages: 4985-4985

    • DOI

      10.1038/s41467-022-32533-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ZO-1 Guides Tight Junction Assembly and Epithelial Morphogenesis via Cytoskeletal Tension-Dependent and -Independent Functions2022

    • Author(s)
      Alexis J Haas, Ceniz Zihni, Susanne M Krug, Riccardo Maraspini, Tetsuhisa Otani, Mikio Furuse, Alf Honigmann, Maria S Balda, Karl Matter
    • Journal Title

      Cells

      Volume: 11 Issue: 23 Pages: 3775-3775

    • DOI

      10.3390/cells11233775

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] EpCAM proteolysis and release of complexed claudin-7 repair and maintain the tight junction barrier2022

    • Author(s)
      Higashi Tomohito、Saito Akira C.、Fukazawa Yugo、Furuse Mikio、Higashi Atsuko Y.、Ono Masahiro、Chiba Hideki
    • Journal Title

      Journal of Cell Biology

      Volume: 222 Issue: 1

    • DOI

      10.1083/jcb.202204079

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angulin-1 seals tricellular contacts independently of tricellulin and claudins2021

    • Author(s)
      Sugawara Taichi、Furuse Kyoko、Otani Tetsuhisa、Wakayama Tomohiko、Furuse Mikio
    • Journal Title

      Journal of Cell Biology

      Volume: 220 Issue: 9

    • DOI

      10.1083/jcb.202005062

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Claudin-9 constitutes tight junctions of folliculo-stellate cells in the anterior pituitary gland2021

    • Author(s)
      Higashi Atsuko Y.、Higashi Tomohito、Furuse Kyoko、Ozeki Kana、Furuse Mikio、Chiba Hideki
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 21642-21642

    • DOI

      10.1038/s41598-021-01004-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [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
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of Claudin-3 Impairs Hepatic Metabolism, Biliary Barrier Function, and Cell Proliferation in the Murine Liver2021

    • Author(s)
      Baier Felix Alexander、Sanchez-Taltavull Daniel、Yarahmadov Tural、Castella Cristina Gomez、Jebbawi Fadi、Keogh Adrian、Tombolini Riccardo、Odriozola Adolfo、Dias Mariana Castro、Deutsch Urban、Furuse Mikio、Engelhardt Britta、Zuber Benoit、Odermatt Alex、Candinas Daniel、Stroka Deborah
    • Journal Title

      Cellular and Molecular Gastroenterology and Hepatology

      Volume: 12 Issue: 2 Pages: 745-767

    • DOI

      10.1016/j.jcmgh.2021.04.003

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] 3細胞結合部位をシールする分子機構2024

    • Author(s)
      古瀬幹夫
    • Organizer
      日本薬学会第144年会シンポジウム[上皮バリアの分子基盤を標的とした創薬研究の最前線]
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Tricellular junctions2023

    • Author(s)
      Mikio Furuse
    • Organizer
      Gordon Research Conference Cell contact and adhesion
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulation of bicellular tight junctions by angulin-12023

    • Author(s)
      Mikio Furuse
    • Organizer
      Tight Junctions: from Structure and Development to Therapeutics
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] How to seal tricellular corners2023

    • Author(s)
      Mikio Furuse
    • Organizer
      DPG 2023 Symposium “Tight junction: Barrier, Channel and More”
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] トリセルラータイトジャンクションの膜タンパク質アンギュリン-1によるタイトジャンクション形成の制御2022

    • Author(s)
      菅原太一,若山友彦, 古瀬幹夫
    • Organizer
      第74回日本細胞生物学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 立体構造に基づく点変異導入を利用したタイトジャンクションタンパク質ZO-1の機能解析2022

    • Author(s)
      藤原佐知子、天野剛志、廣明秀一、古瀬幹夫
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] The roles of claudins and JAM-A in providing tight junction-dependent mechanical resistance.2022

    • Author(s)
      Thanh Phuong Nguyen, Tetsuhisa Otani, Mikio Furuse
    • Organizer
      第74回日本細胞生物学会大会
    • Related Report
      2022 Annual Research Report
  • [Remarks] 生理学研究所細胞構造研究部門

    • URL

      https://www.nips.ac.jp/dcs/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 生理学研究所細胞構造研究部門

    • URL

      http://www.nips.ac.jp/dcs/

    • Related Report
      2022 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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