Mechanical force regulation of YAP by F-actin and GPCR revealed by super-resolution imaging
Mechanical force regulation of YAP by F-actin and GPCR revealed by super-resolution imaging
复制标题
超分辨率成像揭示 F-肌动蛋白和 GPCR 对 YAP 的机械力调节
DOI：
10.1039/c9nr09452k
复制
发表时间：
2020-01-28
期刊：
影响因子：
6.7
通讯作者：
Wang, Hongda
中科院分区：
文献类型：
--
作者：
Gao, Jing;He, Lingli;Wang, Hongda
Hippo信号通路在许多生物学过程中起着关键作用，包括机械转导。该途径的关键激活因子雅普被认为是机械传导信号的中心组分，其感知细胞外机械微环境的变化，如不同的细胞密度、组织结构和基质硬度。虽然已经有大量的研究表明雅普参与了这些过程，但机械力诱导的雅普调节的潜在机制仍不清楚。在这里，我们对细胞表面施加压力，并研究了雅普如何使用超分辨率成像技术之一dSTORM来感知细胞外机械力的变化。我们证明，压力促进F-肌动蛋白解聚，RhoA下调，和LPAR 1（G α 12/13偶联受体）失活，导致雅普胞质易位和减少集群。我们的工作揭示了GPCR和F-actin在压力控制的雅普失活中的作用，并为Hippo信号通路的机械调节机制提供了新的见解。
The Hippo signaling pathway plays critical roles in many biological processes including mechanotransduction. The key activator YAP of this pathway is considered as a central component of mechanotransduction signaling sensing the extracellular mechanical microenvironment changes, such as different cell density, the architecture of tissues and matrix stiffness. Although it has been largely studied that YAP is involved in these processes, the underlying mechanism of mechanical force-induced YAP regulation remains unclear. Here we exerted pressure on cell surfaces and investigated how YAP senses the extracellular mechanical force change using one of the super-resolution imaging techniques, dSTORM. We demonstrated that pressure promoted F-actin depolymerization, RhoA down-regulation, and LPAR1 (G alpha 12/13-coupled receptor) inactivation, which led to YAP cytoplasmic translocation and decreased clustering. Our work uncovers the role of GPCRs and F-actin in pressure-controlled YAP inactivation, and provides new insights into the mechanisms of mechanical regulation of the Hippo signaling pathway.