The Role of PIEZO2 in Human Mechanosensation.
The Role of PIEZO2 in Human Mechanosensation.
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DOI：
10.1056/nejmoa1602812
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发表时间：
2016-10-06
期刊：
影响因子：
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通讯作者：
Bönnemann CG
中科院分区：
文献类型：
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作者：
Chesler AT;Szczot M;Bharucha-Goebel D;Čeko M;Donkervoort S;Laubacher C;Hayes LH;Alter K;Zampieri C;Stanley C;Innes AM;Mah JK;Grosmann CM;Bradley N;Nguyen D;Foley AR;Le Pichon CE;Bönnemann CG
触觉和本体感觉唤起一系列感知，并依赖于检测和识别机械力的能力。这些感觉功能的分子和神经机制仍然不清楚。拉伸门控离子通道PIEZO 2已被证明是必不可少的方面的机械感觉在模式生物。我们对两名具有独特神经肌肉和骨骼症状（包括进行性脊柱侧凸）的患者进行了全外显子组测序分析，这些患者不符合标准诊断分类。在体外和信使RNA测定，功能性脑成像，心理物理和运动测试被用来建立蛋白质功能和躯体感觉的遗传变异的影响。每个患者都携带PIEZO 2中的化合物失活变体，并且每个患者都有选择性丧失辨别性触觉感知，但仍然对多毛皮肤上的特定类型的温和机械刺激做出反应。这些患者的本体感觉明显下降，导致共济失调和辨距障碍，在没有视觉提示的情况下明显更糟。然而，他们有能力执行一系列任务，如走路，说话和写作，这些都被认为严重依赖本体感觉。我们的研究结果表明，PIEZO 2是人类机械感觉的决定因素。（由美国国立卫生研究院校内研究计划资助。
The senses of touch and proprioception evoke a range of perceptions and rely on the ability to detect and transduce mechanical force. The molecular and neural mechanisms underlying these sensory functions remain poorly defined. The stretch-gated ion channel PIEZO2 has been shown to be essential for aspects of mechanosensation in model organisms. We performed whole-exome sequencing analysis in two patients who had unique neuromuscular and skeletal symptoms, including progressive scoliosis, that did not conform to standard diagnostic classification. In vitro and messenger RNA assays, functional brain imaging, and psychophysical and kinematic tests were used to establish the effect of the genetic variants on protein function and somatosensation. Each patient carried compound-inactivating variants in PIEZO2, and each had a selective loss of discriminative touch perception but nevertheless responded to specific types of gentle mechanical stimulation on hairy skin. The patients had profoundly decreased proprioception leading to ataxia and dysmetria that were markedly worse in the absence of visual cues. However, they had the ability to perform a range of tasks, such as walking, talking, and writing, that are considered to rely heavily on proprioception. Our results show that PIEZO2 is a determinant of mechanosensation in humans. (Funded by the National Institutes of Health Intramural Research Program.)