Optogenetic control of RhoA reveals zyxin-mediated elasticity of stress fibres.
Optogenetic control of RhoA reveals zyxin-mediated elasticity of stress fibres.
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DOI：
10.1038/ncomms15817
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发表时间：
2017-06-12
影响因子：
16.6
通讯作者：
Gardel ML
中科院分区：
文献类型：
--
作者：
Oakes PW;Wagner E;Brand CA;Probst D;Linke M;Schwarz US;Glotzer M;Gardel ML
细胞骨架力学调节着细胞形态动力学和许多生理过程。虽然已知收缩性很大程度上依赖于rhoa，但局部生化信号转化为细胞水平反应的过程却知之甚少。在这里，我们结合RhoA的光遗传学控制，活细胞成像和牵引力显微镜来研究基于肌动球蛋白的力产生的动力学。RhoA的局部激活不仅刺激肌动蛋白和肌球蛋白的局部募集，还增加了牵引力，牵引力通过应力纤维在细胞中迅速传播，并推动肌动蛋白流量增加。令人惊讶的是，当局部RhoA激活停止时，这种流动方向相反。我们确定酶是应力纤维力学的调节剂，因为应力纤维是流体状的，在没有酶的情况下没有流动逆转。使用物理模型，我们证明应力纤维表现出弹性样，即使在超过组成蛋白质周转的时间尺度上。这种对肌动蛋白力学的分子控制可能在调节形态动力学事件中起着关键作用。细胞的收缩性是由GTPase RhoA调节的，但是局部信号是如何转化为细胞水平的反应还不清楚。在这里，作者表明靶向RhoA激活导致力沿着应力纤维和肌动蛋白流动传播，并确定酶是应力纤维力学和动态平衡的调节剂。
Cytoskeletal mechanics regulates cell morphodynamics and many physiological processes. While contractility is known to be largely RhoA-dependent, the process by which localized biochemical signals are translated into cell-level responses is poorly understood. Here we combine optogenetic control of RhoA, live-cell imaging and traction force microscopy to investigate the dynamics of actomyosin-based force generation. Local activation of RhoA not only stimulates local recruitment of actin and myosin but also increased traction forces that rapidly propagate across the cell via stress fibres and drive increased actin flow. Surprisingly, this flow reverses direction when local RhoA activation stops. We identify zyxin as a regulator of stress fibre mechanics, as stress fibres are fluid-like without flow reversal in its absence. Using a physical model, we demonstrate that stress fibres behave elastic-like, even at timescales exceeding turnover of constituent proteins. Such molecular control of actin mechanics likely plays critical roles in regulating morphodynamic events. Cellular contractility is regulated by the GTPase RhoA, but how local signals are translated to a cell-level response is not known. Here the authors show that targeted RhoA activation results in propagation of force along stress fibres and actin flow, and identify zyxin as a regulator of stress fibre mechanics and homeostasis.