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<p>Yes-associated protein (YAP), an important downstream mediator of the Hippo pathway, exhibits nuclear translocation when it is dephosphorylated. However, its interplay with other intracellular substances has not yet been clarified. Here, we explored mechano-induced YAP nuclear translocations and its interplay with importin-β (Impβ), one of the nucleocytoplasmic transport receptors, through live imaging of the spatiotemporal distribution of intracellular YAP and Impβ following mechanical stimulation, represented by the release of intercellular tension. YAP nuclear translocation was impeded by inhibition of Impβ and F-actin polymerization. Specifically, inhibiting F-actin polymerization not only impeded the nuclear import of YAP but also prevented its translocation from the near regions, adjacent to the wounded cell, toward the nucleus. These results provide a fundamental basis for further research into mechanotransduction, particularly mechano-induced YAP translocation, and may potentially be exploited as a therapeutic target for wound healing.</p>

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Spatiotemporal distribution of YAP and importin-β in nucleus and cytosol after wounding of adjacent cells

  • 期刊论文

  • 发表日期：

    2025年5月29日

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  • Boyuan Xiao,
  • Saori Sasaki,
  • Naoki Takeishi,
  • Toshihiro Sera,
  • Susumu Kudo

摘要

Yes-associated protein (YAP), an important downstream mediator of the Hippo pathway, exhibits nuclear translocation when it is dephosphorylated. However, its interplay with other intracellular substances has not yet been clarified. Here, we explored mechano-induced YAP nuclear translocations and its interplay with importin-β (Impβ), one of the nucleocytoplasmic transport receptors, through live imaging of the spatiotemporal distribution of intracellular YAP and Impβ following mechanical stimulation, represented by the release of intercellular tension. YAP nuclear translocation was impeded by inhibition of Impβ and F-actin polymerization. Specifically, inhibiting F-actin polymerization not only impeded the nuclear import of YAP but also prevented its translocation from the near regions, adjacent to the wounded cell, toward the nucleus. These results provide a fundamental basis for further research into mechanotransduction, particularly mechano-induced YAP translocation, and may potentially be exploited as a therapeutic target for wound healing.