Myosin-II mediated traction forces evoke localized Piezo1-dependent Ca2+ flickers.,Communications Biology

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Myosin-II mediated traction forces evoke localized Piezo1-dependent Ca2+ flickers.
Communications Biology ( IF 5.2 ) Pub Date : 2019-08-07 , DOI: 10.1038/s42003-019-0514-3
Kyle L Ellefsen ₁ , Jesse R Holt _{2,

3,

4} , Alice C Chang ₅ , Jamison L Nourse _{2,

3} , Janahan Arulmoli _{3,

6} , Armen H Mekhdjian ₅ , Hamid Abuwarda _{2,

3} , Francesco Tombola ₂ , Lisa A Flanagan _{3,

6,

7} , Alexander R Dunn _{5,

8} , Ian Parker _{1,

2} , Medha M Pathak _{2,

3,

4,

6}

Affiliation

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.

中文翻译：

肌球蛋白-II 介导的牵引力引起局部 Piezo1 依赖性 Ca2+ 闪烁。

压电通道将机械刺激转换为电信号和化学信号，从而强烈影响发育、组织稳态和再生。对 Piezo1 的研究主要集中在“由外向内”机械力的转导上，而其对细胞产生的内部力的反应仍然知之甚少。在这里，通过测量天然细胞条件下的内源性 Piezo1 活性和牵引力，我们发现在没有外部施加机械力的情况下，细胞牵引力会产生空间限制的 Piezo1 介导的 Ca2+ 闪烁。尽管 Piezo1 通道很容易在质膜中扩散并且广泛分布在整个细胞中，但它们的闪烁活动在产生力的粘附附近丰富。激活 Piezo1 的机械力源自肌球蛋白轻链激酶对肌球蛋白 II 的磷酸化。我们认为 Piezo1 Ca2+ 闪烁允许机械转导事件的空间分离，并且移动性允许 Piezo1 通道探索大量机械微域，从而对更多样化的机械线索做出反应。

更新日期：2019-08-07

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