TMEM25 is a Par3-binding protein that attenuates claudin assembly during tight junction development

書誌事項

公開日
2023-12-18
資源種別
journal article
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1038/s44319-023-00018-0
公開者
Springer Science and Business Media LLC

説明

<jats:title>Abstract</jats:title> <jats:p> The tight junction (TJ) in epithelial cells is formed by integral membrane proteins and cytoplasmic scaffolding proteins. The former contains the claudin family proteins with four transmembrane segments, while the latter includes Par3, a PDZ domain-containing adaptor that organizes TJ formation. Here we show the single membrane-spanning protein TMEM25 localizes to TJs in epithelial cells and binds to Par3 via a PDZ-mediated interaction with its C-terminal cytoplasmic tail. TJ development during epithelial cell polarization is accelerated by depletion of TMEM25, and delayed by overexpression of TMEM25 but not by that of a C-terminally deleted protein, indicating a regulatory role of TMEM25. TMEM25 associates via its N-terminal extracellular domain with claudin-1 and claudin-2 to suppress their <jats:italic>cis</jats:italic> - and <jats:italic>trans</jats:italic> -oligomerizations, both of which participate in TJ strand formation. Furthermore, Par3 attenuates TMEM25–claudin association via binding to TMEM25, implying its ability to affect claudin oligomerization. Thus, the TJ protein TMEM25 appears to negatively regulate claudin assembly in TJ formation, which regulation is modulated by its interaction with Par3. </jats:p>

収録刊行物

  • EMBO Reports

    EMBO Reports 25 (1), 144-167, 2023-12-18

    Springer Science and Business Media LLC

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