PIEZO2在人类机械感觉中的作用。
The Role of PIEZO2 in Human Mechanosensation.
作者信息
Chesler Alexander T, Szczot Marcin, Bharucha-Goebel Diana, Čeko Marta, Donkervoort Sandra, Laubacher Claire, Hayes Leslie H, Alter Katharine, Zampieri Cristiane, Stanley Christopher, Innes A Micheil, Mah Jean K, Grosmann Carla M, Bradley Nathaniel, Nguyen David, Foley A Reghan, Le Pichon Claire E, Bönnemann Carsten G
机构信息
From the National Center for Complementary and Integrative Health (A.T.C., M.S., M.C., C.L.), the National Institute of Neurological Disorders and Stroke (D.B.-G., S.D., L.H.H., N.B., D.N., A.R.F., C.E.L.P., C.G.B.), and the Functional and Applied Biomechanics Section, Rehabilitation Medicine Department, Clinical Center (K.A., C.Z., C.S.), National Institutes of Health, Bethesda, MD; the Division of Neurology, Children's National Health System, Washington, DC (D.B.-G.); the Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine (A.M.I.), and the Department of Clinical Neurosciences and Department of Pediatrics, Alberta Children's Hospital Research Institute (J.K.M.), University of Calgary, Calgary, Canada; and the Departments of Neurosciences and Pediatrics, School of Medicine, University of California, San Diego, Rady Children's Hospital, San Diego, CA (C.M.G.).
出版信息
N Engl J Med. 2016 Oct 6;375(14):1355-1364. doi: 10.1056/NEJMoa1602812. Epub 2016 Sep 21.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
Our results show that PIEZO2 is a determinant of mechanosensation in humans. (Funded by the National Institutes of Health Intramural Research Program.).
背景
触觉和本体感觉能引发一系列感知，且依赖于检测和转换机械力的能力。这些感觉功能背后的分子和神经机制仍未完全明确。拉伸门控离子通道PIEZO2已被证明在模式生物的机械感觉方面至关重要。
方法
我们对两名患有独特神经肌肉和骨骼症状（包括进行性脊柱侧弯）的患者进行了全外显子组测序分析，这些症状不符合标准诊断分类。采用体外和信使核糖核酸分析、功能性脑成像以及心理物理学和运动学测试来确定基因变异对蛋白质功能和躯体感觉的影响。
结果
每名患者都携带PIEZO2的复合失活变异，且均有辨别性触觉感知的选择性丧失，但对多毛皮肤上特定类型的轻柔机械刺激仍有反应。患者的本体感觉严重下降，导致共济失调和辨距不良，在没有视觉线索时情况明显更糟。然而，他们有能力执行一系列被认为严重依赖本体感觉的任务，如行走、说话和写作。
结论
我们的结果表明PIEZO2是人类机械感觉的一个决定因素。（由美国国立卫生研究院内部研究项目资助。）
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