In the context of mechanically induced force transmission, the modification of the actin cytoskeleton through involvement of zyxin is an established concept. However, in cells of the periodontal ligament (PDL), which is physiologically subjected to intermittent mechanical forces, the force-responsive modulation of zyxin and the molecular key players, which orchestrate its cellular regulation, have not yet been elucidated. By employing indirect immunofluorescence and western blotting with different subcellular fractions, we show here in stretch force-exposed human PDL fibroblasts (hPDLFs) that (i) the zyxin protein is modulated, and (ii) its subcellular localization is altered. More importantly, using a pharmacological intervention approach, to inhibit the nuclear presence of the co-transcriptional activator yes-associated protein (YAP), we evidence for the first time that on the molecular level, the cellular abundance of zyxin, among the Thyrotrophic Embryonic Factor (TEF)-binding proteins, is regulated by YAP rather than TAZ. Our findings provide novel insights into the topic how cells of the periodontium and the periodontal ligament in particular respond and may adapt to mechanical forces, and first time identify YAP as the key player of the intracellular regulation of the mechano-sensor and mechano-transducer zyxin in hPDLFs. Moreover, the findings broaden the current knowledge on YAP, since so far, currently only very few YAP-regulated genes have been identified.

中文翻译：

---

牙周膜细胞中的力响应性 Zyxin 调节受 YAP 而非 TAZ 调节。

在机械诱导力传递的背景下，通过 zyxin 的参与来修饰肌动蛋白细胞骨架是一个既定的概念。然而，在生理上受到间歇性机械力的牙周膜 (PDL) 细胞中，zyxin 的力响应调节和协调其细胞调节的分子关键参与者尚未阐明。通过使用不同亚细胞组分的间接免疫荧光和蛋白质印迹，我们在拉伸力暴露的人类 PDL 成纤维细胞 (hPDLF) 中显示 (i) zyxin 蛋白被调节，以及 (ii) 其亚细胞定位被改变。更重要的是，使用药理学干预方法，抑制共转录激活因子是相关蛋白 (YAP) 的核存在，我们首次证明，在分子水平上，在甲状腺营养胚胎因子 (TEF) 结合蛋白中，zyxin 的细胞丰度受 YAP 而非 TAZ 调节。我们的研究结果为牙周细胞和牙周韧带细胞如何特别响应并可能适应机械力这一主题提供了新见解，并首次将 YAP 确定为机械传感器和机械传感器 zyxin 的细胞内调节的关键参与者在 hPDLF 中。此外，这些发现拓宽了目前对 YAP 的认识，因为到目前为止，目前仅鉴定了很少的 YAP 调节基因。我们的研究结果为牙周细胞和牙周膜细胞如何特别响应并可能适应机械力这一主题提供了新见解，并首次将 YAP 确定为机械传感器和机械传感器 zyxin 细胞内调节的关键参与者在 hPDLF 中。此外，这些发现拓宽了目前对 YAP 的认识，因为到目前为止，目前仅鉴定了很少的 YAP 调节基因。我们的研究结果为牙周细胞和牙周膜细胞如何特别响应并可能适应机械力这一主题提供了新见解，并首次将 YAP 确定为机械传感器和机械传感器 zyxin 细胞内调节的关键参与者在 hPDLF 中。此外，这些发现拓宽了目前对 YAP 的认识，因为到目前为止，目前仅鉴定了很少的 YAP 调节基因。