Piezo2 is the major transducer of mechanical forces for touch sensation in mice.
Piezo2 is the major transducer of mechanical forces for touch sensation in mice.
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DOI：
10.1038/nature13980
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发表时间：
2014-12-04
期刊：
影响因子：
64.8
通讯作者：
Patapoutian, Ardem
中科院分区：
文献类型：
--
作者：
Ranade, Sanjeev S.;Woo, Seung-Hyun;Dubin, Adrienne E.;Moshourab, Rabih A.;Wetzel, Christiane;Petrus, Matt;Mathur, Jayanti;Begay, Valerie;Coste, Bertrand;Mainquist, James;Wilson, A. J.;Francisco, Allain G.;Reddy, Kritika;Qiu, Zhaozhu;Wood, John N.;Lewin, Gary R.;Patapoutian, Ardem
触觉通过将机械能转化为电信号来提供有关我们物理环境的关键信息。据推测，机械激活（MA）阳离子通道启动触觉，但这些分子在哺乳动物中的身份一直难以捉摸。Piezo 2是在背根神经节（DRG）的感觉神经元的子集和被称为默克尔细胞-神经突复合物的皮肤机械感受器中表达的快速适应（RA）MA离子通道。默克尔细胞已被证明在使用Piezo 2的脊椎动物机械感觉中发挥作用，特别是在塑造由其支配的感觉神经元发送的电流类型中。然而，触觉的主要方面在没有默克尔细胞活性的情况下保持完整。在这里，我们发现，在成年感觉神经元和默克尔细胞中缺乏Piezo 2的小鼠表现出严重的触觉丧失。我们将Piezo 2精确定位于广泛的低阈值机械感受器（LTMR）的外周末梢，这些机械感受器支配多毛和无毛皮肤。Piezo 2CKO小鼠DRG神经元培养物中的大多数RA MA电流不存在，并且离体皮肤神经制备研究表明LTMR的机械敏感性强烈依赖于Piezo 2。这种引人注目的细胞表型与前所未有的行为表型相关：在多种行为测定中几乎完全缺乏光触觉，而不影响其他躯体感觉功能。我们的研究结果强调，一个单一的离子通道，显示RA MA电流在体外是负责大多数LTMR亚型参与无害的触觉的机械敏感性。有趣的是，我们发现触摸和疼痛感觉是可分离的，这表明未知的MA离子通道必须解释有害的（疼痛的）机械感觉。
The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals. It is postulated that mechanically activated (MA) cation channels initiate touch sensation, but the identity of these molecules in mammals has been elusive. Piezo2 is a rapidly adapting (RA) MA ion channel expressed in a subset of sensory neurons of the dorsal root ganglion (DRG) and in cutaneous mechanoreceptors known as Merkel cell-neurite complexes. Merkel cells have been demonstrated to play a role in vertebrate mechanosensation using Piezo2, particularly in shaping the type of current sent by its innervating sensory neuron. However, major aspects of touch sensation remain intact without Merkel cell activity. Here, we show that mice lacking Piezo2 in both adult sensory neurons and Merkel cells exhibit a profound loss of touch sensation. We precisely localize Piezo2 to the peripheral endings of a broad range of low threshold mechanoreceptors (LTMRs) that innervate both hairy and glabrous skin. Most RA MA currents in DRG neuronal cultures are absent in Piezo2CKO mice, and ex vivo skin nerve preparation studies show that mechanosensitivity of LTMRs strongly depends on Piezo2. This striking cellular phenotype correlates with an unprecedented behavioral phenotype: an almost complete deficit in light touch sensation in multiple behavioral assays, without affecting other somatosensory functions. Our results highlight that a single ion channel that displays RA MA currents in vitro is responsible for the mechanosensitivity of most LTMR subtypes involved in innocuous touch sensation. Interestingly, we find that touch and pain sensation are separable, suggesting that yet-unknown MA ion channel(s) must account for noxious (painful) mechanosensation.
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影响因子：
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