Xiao Boyuan, Sasaki Saori, Takeishi Naoki, Sera Toshihiro, Kudo Susumu
Department of Mechanical Engineering, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, Fukuoka, 819-0395, Japan.
Department of Mechanical Engineering, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka, Fukuoka, 819-0395, Japan.
In Vitro Cell Dev Biol Anim. 2025 May 29. doi: 10.1007/s11626-025-01054-x.
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.
Yes相关蛋白（YAP）是Hippo信号通路的重要下游介质，去磷酸化时会发生核转位。然而，其与其他细胞内物质的相互作用尚未阐明。在此，我们通过对机械刺激（以细胞间张力释放为代表）后细胞内YAP和核转运蛋白β（Impβ）之一的时空分布进行实时成像，探索了机械诱导的YAP核转位及其与Impβ的相互作用。抑制Impβ和F-肌动蛋白聚合可阻碍YAP核转位。具体而言，抑制F-肌动蛋白聚合不仅会阻碍YAP的核输入，还会阻止其从受伤细胞相邻的附近区域向细胞核的转位。这些结果为进一步研究机械转导，特别是机械诱导的YAP转位提供了基础，并有可能被用作伤口愈合的治疗靶点。
