YAP regulates cell mechanics by controlling focal adhesion assembly.
YAP regulates cell mechanics by controlling focal adhesion assembly.
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DOI：
10.1038/ncomms15321
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发表时间：
2017-05-15
影响因子：
16.6
通讯作者：
Forte G
中科院分区：
文献类型：
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作者：
Nardone G;Oliver-De La Cruz J;Vrbsky J;Martini C;Pribyl J;Skládal P;Pešl M;Caluori G;Pagliari S;Martino F;Maceckova Z;Hajduch M;Sanz-Garcia A;Pugno NM;Stokin GB;Forte G
河马效应器YAP/TAZ通过感知细胞外基质(ECM)组成和力学的变化，起到开关机械传感的作用。其活性的调节由一个分层模型描述，在该模型中，河马途径的元件受焦点粘连(FA)的控制。在这里，我们揭示了细胞伸展和RhoA GTPase活性通过YAP控制FA形成的分子机制，以稳定肌动蛋白细胞骨架与细胞膜的锚定。这一机制需要YAP共转录功能，并涉及编码整合素和FA对接蛋白的基因的激活。调节YAP转录活性导致细胞力学、力量发育和黏附强度的改变，并决定细胞的形状、迁移和分化。这些结果为YAP机械传感活动的机制提供了新的见解，并使该河马效应器成为响应ECM信号的细胞力学的关键决定因素。已知转录共激活因子YAP在细胞生态位产生的机械信号的下游起作用。在这里，作者证明了YAP通过促进与局部粘连相关的基因的转录来控制细胞力学、力量发育和粘连强度。
Hippo effectors YAP/TAZ act as on–off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described by a hierarchical model in which elements of Hippo pathway are under the control of focal adhesions (FAs). Here we unveil the molecular mechanism by which cell spreading and RhoA GTPase activity control FA formation through YAP to stabilize the anchorage of the actin cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional function and involves the activation of genes encoding for integrins and FA docking proteins. Tuning YAP transcriptional activity leads to the modification of cell mechanics, force development and adhesion strength, and determines cell shape, migration and differentiation. These results provide new insights into the mechanism of YAP mechanosensing activity and qualify this Hippo effector as the key determinant of cell mechanics in response to ECM cues. The transcriptional co-activator YAP is known to operate downstream of mechanical signals arising from the cell niche. Here the authors demonstrate that YAP controls cell mechanics, force development and adhesion strength by promoting the transcription of genes related to focal adhesions.