Shear stress activates nociceptors to drive Drosophila mechanical nociception
Shear stress activates nociceptors to drive Drosophila mechanical nociception
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DOI：
10.1016/j.neuron.2022.08.015
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发表时间：
2022-11-16
期刊：
影响因子：
16.2
通讯作者：
Xiang, Yang
中科院分区：
文献类型：
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作者：
Gong, Jiaxin;Chen, Jiazhang;Xiang, Yang
机械伤害感对于动物的生存是必不可少的。然而，参与伤害性感受器激活的力量和潜在的机械转导机制仍然难以捉摸。在这里，我们通过研究果蝇幼虫的致病行为来解决这些问题。我们表明，强烈的戳刺激伤害性感受器的混合力，包括剪应力和拉伸。出乎意料的是，伤害性感受器选择性地被剪切力激活，而不是拉伸。伤害性感受器的切应力反应和伤害性行为都需要瞬时受体电位A1(TRPA1)，它在伤害性感受器中特异表达。我们进一步证明，哺乳动物或果蝇TRPA1在异源细胞中的表达对剪应力有反应，但对拉伸没有反应。最后，剪切力通过调节膜流动性，以膜分隔的方式激活TRPA1。综上所述，我们的研究揭示了TRPA1是一种进化上保守的机械敏感通道，由剪切力特异地激活，并提示剪切力在激活伤害性感受器以驱动机械伤害性感受中起着关键作用。
Mechanical nociception is essential for animal survival. However, the forces involved in nociceptor activation and the underlying mechanotransduction mechanisms remain elusive. Here, we address these problems by investigating nocifensive behavior in Drosophila larvae. We show that strong poking stimulates nociceptors with a mixture of forces including shear stress and stretch. Unexpectedly, nociceptors are selectively activated by shear stress, but not stretch. Both the shear stress responses of nociceptors and nocifensive behavior require transient receptor potential A1 (TrpA1), which is specifically expressed in nociceptors. We further demonstrate that expression of mammalian or Drosophila TrpA1 in heterologous cells confers responses to shear stress but not stretch. Finally, shear stress activates TrpA1 in a membrane-delimited manner, through modulation of membrane fluidity. Together, our study reveals TrpA1 as an evolutionarily conserved mechanosensitive channel specifically activated by shear stress and suggests a critical role of shear stress in activating nociceptors to drive mechanical nociception.