Piezo2 is required for Merkel-cell mechanotransduction.
Piezo2 is required for Merkel-cell mechanotransduction.
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DOI：
10.1038/nature13251
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发表时间：
2014-05-29
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：
Woo, Seung-Hyun;Ranade, Sanjeev;Weyer, Andy D.;Dubin, Adrienne E.;Baba, Yoshichika;Qiu, Zhaozhu;Petrus, Matt;Miyamoto, Takashi;Reddy, Kritika;Lumpkin, Ellen A.;Stucky, Cheryl L.;Patapoutian, Ardem
我们如何感知触觉仍然是未知的。默克尔细胞-神经突复合体是皮肤中的一种温和的触觉感受器，可介导 Aβ 感觉纤维的缓慢适应 (SA) 反应，以编码物体的精细细节。近 50 年前，人们认识到这种机械感受器复合体在感知轻柔触摸方面发挥着重要作用。然而，默克尔细胞或传入纤维本身是否感知机械力仍存在争议，力传导的分子机制尚不清楚。有趣的是，在默克尔细胞和相关传入神经之间观察到类似突触的连接，但尚不清楚默克尔细胞是否本质上具有机械敏感性，或者它们是否可以快速将此类信息传递到邻近的神经。在这里，我们首次证明默克尔细胞在体外产生触摸感应电流。 Piezo2 是一种机械激活 (MA) 阳离子通道，在默克尔细胞中表达。我们对皮肤中缺乏 Piezo2 的小鼠进行了改造，但感觉神经元中没有，并表明默克尔细胞的机械敏感性完全依赖于 Piezo2。在这些小鼠中，默克尔细胞-神经突复合物介导的体内 SA 反应表现出静态放电率降低，而且，它们对轻柔触摸的行为反应适度降低。我们的结果表明 Piezo2 是默克尔细胞机械传导通道，并提供了压电在哺乳动物机械感觉中发挥生理作用的第一线证据。此外，我们的数据提供了双受体位点模型的证据，其中默克尔细胞和神经传入神经协同作用作为机械传感器。双感受器系统可以为这种机械感受器复合体提供调节机制，以实现对给定机械刺激的高度复杂的响应。
How we sense touch remains fundamentally unknown. The Merkel cell-neurite complex is a gentle touch receptor in the skin that mediates slowly-adapting (SA) responses of Aβ sensory fibers to encode fine details of objects. This mechanoreceptor complex was recognized to play an essential role in sensing gentle touch nearly 50 years ago. However, whether Merkel cells or afferent fibers themselves sense mechanical force is still debated, and the molecular mechanism of mechanotransduction is unknown. Interestingly, synapse-like junctions are observed between Merkel cells and associated afferents, and yet it is unclear if Merkel cells are inherently mechanosensitive or whether they can rapidly transmit such information to the neighboring nerve. Here we show for the first time that Merkel cells produce touch-sensitive currents in vitro. Piezo2, a mechanically-activated (MA) cation channel, is expressed in Merkel cells. We engineered mice deficient in Piezo2 in the skin, but not in sensory neurons, and show that Merkel cell mechanosensitivity completely depends on Piezo2. In these mice, Merkel cell-neurite complex-mediated SA responses in vivo show reduced static firing rates, and moreover, they display moderately decreased behavioral responses to gentle touch. Our results indicate that Piezo2 is the Merkel cell mechanotransduction channel and provide the first line of evidence that Piezos play a physiological role in mechanosensation in mammals. Furthermore, our data present evidence for a two-receptor site model, where both Merkel cells and innervating afferents act in concert as mechanosensors. The two-receptor system could provide this mechanoreceptor complex with a tuning mechanism to achieve highly sophisticated responses to a given mechanical stimulus.
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影响因子：
3.3
作者：
Petrus M;Peier AM;Bandell M;Hwang SW;Huynh T;Olney N;Jegla T;Patapoutian A
通讯作者：
Patapoutian A
影响因子：
2.5
作者：
Koltzenburg, M;Stucky, CL;Lewin, GR
通讯作者：
Lewin, GR
影响因子：
5.5
作者：
IKEDA, I;YAMASHITA, Y;OGAWA, H
通讯作者：
OGAWA, H
DOI：
10.1126/science.1172890
发表时间：
2009-06-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Maricich SM;Wellnitz SA;Nelson AM;Lesniak DR;Gerling GJ;Lumpkin EA;Zoghbi HY
通讯作者：
Zoghbi HY
影响因子：
64.8
作者：
Coste, Bertrand;Xiao, Bailong;Santos, Jose S.;Syeda, Ruhma;Grandl, Joerg;Spencer, Kathryn S.;Kim, Sung Eun;Schmidt, Manuela;Mathur, Jayanti;Dubin, Adrienne E.;Montal, Mauricio;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem