Myosin-II mediated traction forces evoke localized Piezo1-dependent Ca2+ flickers
Myosin-II mediated traction forces evoke localized Piezo1-dependent Ca2+ flickers
复制标题
DOI：
10.1038/s42003-019-0514-3
复制
发表时间：
2019-08-07
影响因子：
5.9
通讯作者：
Pathak, Medha M.
中科院分区：
文献类型：
--
作者：
Ellefsen, Kyle L.;Holt, Jesse R.;Pathak, Medha M.
压电通道将机械刺激转化为电信号和化学信号，从而有力地影响发育、组织动态平衡和再生。对Piezo1的研究主要集中在由外而内的机械力的传递上，而它对内部细胞产生的力的反应仍然知之甚少。在这里，通过测量自然细胞条件下内源性Piezo1的活性和牵引力，我们证明了在没有外部机械力的情况下，细胞牵引力产生空间受限的Piezo1介导的钙闪烁。尽管Piezo1通道很容易在质膜中扩散，并广泛分布于整个细胞，但它们的闪烁活性在产生力的粘连附近得到了丰富。激活Piezo1的机械力来自肌球蛋白轻链激酶对肌球蛋白II的磷酸化。我们认为，Piezo1钙离子闪烁允许机械转导事件的空间分离，而迁移性允许Piezo1通道探索大量的机械微域，从而对更多多样性的机械信号做出反应。
Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, tissue homeostasis, and regeneration. Studies on Piezo1 have largely focused on transduction of "outside-in" mechanical forces, and its response to internal, cell-generated forces remains poorly understood. Here, using measurements of endogenous Piezo1 activity and traction forces in native cellular conditions, we show that cellular traction forces generate spatially-restricted Piezo1-mediated Ca2+ flickers in the absence of externally-applied mechanical forces. Although Piezo1 channels diffuse readily in the plasma membrane and are widely distributed across the cell, their flicker activity is enriched near force-producing adhesions. The mechanical force that activates Piezo1 arises from Myosin II phosphorylation by Myosin Light Chain Kinase. We propose that Piezo1 Ca2+ flickers allow spatial segregation of mechanotransduction events, and that mobility allows Piezo1 channels to explore a large number of mechanical microdomains and thus respond to a greater diversity of mechanical cues.