The role of Drosophila Piezo in mechanical nociception.
The role of Drosophila Piezo in mechanical nociception.
复制标题
果蝇压电在机械伤害感受中的作用。
DOI：
10.1038/nature10801
复制
发表时间：
2012-02-19
期刊：
影响因子：
64.8
通讯作者：
Patapoutian A
中科院分区：
文献类型：
--
作者：
Kim SE;Coste B;Chadha A;Cook B;Patapoutian A
机械刺激的转导由受体神经元是必不可少的感觉，如听觉，触觉和疼痛。离子通道在无脊椎动物神经元机械转导中的作用然而，没有观察到这些离子通道在哺乳动物机械转导中的功能守恒。例如，在黑胃果蝇和秀丽隐杆线虫中，TRP离子通道NOMPC作为机械传感器；然而，它在哺乳动物中没有同源物。DEG/ENaC家族成员是秀丽隐杆线虫的机械传感器，也可能是黑腹线虫的机械传感器；然而，其哺乳动物同源物在感知机械力方面的直接作用尚未显示。最近，Piezo1和Piezo2被鉴定为哺乳动物机械激活（MA）通道的组成部分。Piezos代表了一个进化保守的跨膜蛋白家族。目前尚不清楚压电是否在体内的机械感觉中起作用，如果起作用，它们介导的机械感觉模式是什么。在这里，我们研究了单压电体在d.m elanogaster （pipiezo）中的生理作用。人类细胞中的piiezo表达诱导机械激活电流，与哺乳动物相似[Coste等人，随附论文]。对有害机械刺激的行为反应严重降低，而对其他有害刺激或触摸的反应不受影响。敲除介导伤害感觉的感觉神经元中的pipiezo和表达DEG/ENaC离子通道扒手（ppk）足以损害对有害机械刺激的反应。此外，在这些相同的神经元中，dpiezo的表达挽救了组成型dpiezo敲除幼虫的表型。因此，来自ppk阳性神经元的电生理记录显示了一个依赖于pipiezo的机械激活电流。最后，我们发现在ppk阳性细胞中，piiezo和ppk在平行通路中起作用，并且在缺乏这两个通道的情况下，机械性伤害感觉被消除。这些数据证明了压电家族在体内机械转导中的生理相关性，支持压电蛋白在机械感觉伤害感受中的作用。
Transduction of mechanical stimuli by receptor neurons is essential for senses such as hearing, touch, and pain. Ion channels play a role in neuronal mechanotransduction in invertebrates; however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, NOMPC, a TRP ion channel, acts as a mechanotransducer in Drosophila melanogaster and Caenorhabditis elegans; however, it has no orthologues in mammals. DEG/ENaC family members are mechanotransducers in C. elegans and potentially in D. melanogaster; however, a direct role of its mammalian homologues in sensing mechanical force is not shown. Recently, Piezo1 and Piezo2 were identified as components of mechanically activated (MA) channels in mammals. Piezos represent an evolutionary conserved family of transmembrane proteins. It is unknown whether Piezos function in mechanical sensing in vivo, and if they do, which mechanosensory modalities they mediate. Here, we study the physiological role of the single Piezo member in D. melanogaster (dpiezo). dpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts [Coste et al., accompanying paper]. Behavioral responses to noxious mechanical stimuli were severely reduced in dpiezo knockout larvae, while responses to another noxious stimulus or touch were not affected. Knocking down dpiezo in sensory neurons that mediate nociception and express the DEG/ENaC ion channel pickpocket (ppk) was sufficient to impair responses to noxious mechanical stimuli. Furthermore, expression of dpiezo in these same neurons rescued the phenotype of the constitutive dpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a dpiezo dependent, mechanically-activated current. Finally, we found that dpiezo and ppk function in parallel pathways in ppk-positive cells, and that mechanical nociception is abolished in the absence of both channels. These data demonstrate physiological relevance of Piezo family in mechanotransduction in vivo, supporting a role of Piezo proteins in mechanosensory nociception.