2025/05/09 更新

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写真a

チヨウ ユウマ
長 佑磨
CHO YUMA
所属
医学研究院 基礎医学部門 助教
職名
助教

論文

  • A sustained calcium response mediated by IP3 receptor anchoring to the desmosome is essential for apoptotic cell elimination

    Cho, Y; Koyama-Honda, I; Tanimura, A; Matsuzawa, K; Ikenouchi, J

    CURRENT BIOLOGY   34 ( 20 )   4835 - 4844.e4   2024年10月   ISSN:0960-9822 eISSN:1879-0445

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    記述言語:英語   出版者・発行元:Current Biology  

    Efficient elimination of apoptotic cells within epithelial cell sheets is crucial for preserving epithelial barrier integrity.1 It is well established that immediate neighbors of an apoptotic cell actively participate in its removal by enclosing it within a wall of actomyosin, pushing it out in a purse-string manner in a process called apical extrusion.2,3,4,5,6,7 Here, we found that sustained elevation of calcium ions in neighboring epithelial cells is necessary to generate the contractility required for apoptotic cell elimination. This phenomenon, which we call calcium response in effectors of apical extrusion (CaRE), highlights the disparate calcium dynamics within the epithelial sheet. Furthermore, we elucidate the essential role of desmosomes in CaRE. Specifically, we identify a subset of IP3 receptors within the endoplasmic reticulum that is recruited to the desmosome by K-Ras-induced actin-binding protein as the core component of this process. The interplay between these cellular structures heightens actomyosin contractility to drive apoptotic cell removal. Our findings underscore the physiological significance of integrating desmosomes with the endoplasmic reticulum in epithelial sheet homeostasis, shedding new light on cell-cell communication and tissue maintenance.

    DOI: 10.1016/j.cub.2024.08.057

    Web of Science

    Scopus

    PubMed

  • Tricellulin secures the epithelial barrier at tricellular junctions by interacting with actomyosin

    Cho, YM; Haraguchi, D; Shigetomi, K; Matsuzawa, K; Uchida, S; Ikenouchi, J

    JOURNAL OF CELL BIOLOGY   221 ( 4 )   2022年3月   ISSN:0021-9525 eISSN:1540-8140

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    記述言語:英語   出版者・発行元:Journal of Cell Biology  

    The epithelial cell sheet functions as a barrier to prevent invasion of pathogens. It is necessary to eliminate intercellular gaps not only at bicellular junctions, but also at tricellular contacts, where three cells meet, to maintain epithelial barrier function. To that end, tight junctions between adjacent cells must associate as closely as possible, particularly at tricellular contacts. Tricellulin is an integral component of tricellular tight junctions (tTJs), but the molecular mechanism of its contribution to the epithelial barrier function remains unclear. In this study, we revealed that tricellulin contributes to barrier formation by regulating actomyosin organization at tricellular junctions. Furthermore, we identified α-catenin, which is thought to function only at adherens junctions, as a novel binding partner of tricellulin. α-catenin bridges tricellulin attachment to the bicellular actin cables that are anchored end-on at tricellular junctions. Thus, tricellulin mobilizes actomyosin contractility to close the lateral gap between the TJ strands of the three proximate cells that converge on tricellular junctions.

    DOI: 10.1083/jcb.202009037

    Web of Science

    Scopus

    PubMed

講演・口頭発表等

共同研究・競争的資金等の研究課題

  • 上皮細胞における三細胞間密着結合の機能解明

    研究課題/領域番号:23KJ1689  2023年4月 - 2025年3月

    科学研究費助成事業  特別研究員奨励費

    長 佑磨

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    資金種別:科研費

    我々の体や器官の表面を覆う上皮細胞シートは、外界からの異物の侵入や水やイオンの漏出を防ぐバリアとして機能する。このバリア機能の分子的実体は、タイトジャンクションと呼ばれる細胞間接着構造である。タイトジャンクションの破綻は、バリア機能に異常が生じ、アトピー性皮膚炎や炎症性腸疾患の原因となる。上皮細胞シートにおいて、二細胞間だけでなく、三細胞間領域においても、密に細胞同士が接着する必要があるが、二細胞間に比べて、三細胞間領域の接着形成機構は不明な点が多い。本研究では、三細胞間での細胞間接着機構の解明を目指す。

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