Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Research Group on Molecular, Cellular and Genomic Biomedicine Health Research, Institute La Fe and Joint Unit for Rare Diseases CIPF-IIS La Fe, Valencia, Spain.
Nat Neurosci. 2021 Jan;24(1):74-81. doi: 10.1038/s41593-020-00751-y. Epub 2020 Dec 7.
Fingertip mechanoreceptors comprise sensory neuron endings together with specialized skin cells that form the end-organ. Exquisitely sensitive, vibration-sensing neurons are associated with Meissner's corpuscles in the skin. In the present study, we found that USH2A, a transmembrane protein with a very large extracellular domain, was found in terminal Schwann cells within Meissner's corpuscles. Pathogenic USH2A mutations cause Usher's syndrome, associated with hearing loss and visual impairment. We show that patients with biallelic pathogenic USH2A mutations also have clear and specific impairments in vibrotactile touch perception, as do mutant mice lacking USH2A. Forepaw rapidly adapting mechanoreceptors innervating Meissner's corpuscles, recorded from Ush2a mice, showed large reductions in vibration sensitivity. However, the USH2A protein was not found in sensory neurons. Thus, loss of USH2A in corpuscular end-organs reduced mechanoreceptor sensitivity as well as vibration perception. Thus, a tether-like protein is required to facilitate detection of small-amplitude vibrations essential for the perception of fine-grained tactile surfaces.
指尖机械感受器包括感觉神经元末梢和形成末端器官的特殊皮肤细胞。对振动敏感的神经元与皮肤中的梅克尔小体有关。在本研究中，我们发现，USH2A 是一种跨膜蛋白，其细胞外结构域非常大，存在于梅克尔小体的终末施万细胞内。致病性 USH2A 突变会导致 Usher 综合征，伴有听力损失和视力障碍。我们发现，具有双等位致病性 USH2A 突变的患者也存在明显且特定的振动触觉感知障碍，缺乏 USH2A 的突变小鼠也是如此。从 Ush2a 小鼠中记录到的支配梅克尔小体的前爪快速适应机械感受器，其振动敏感性显著降低。然而，在感觉神经元中没有发现 USH2A 蛋白。因此，颗粒状末端器官中 USH2A 的缺失降低了机械感受器的敏感性以及振动感知能力。因此，需要一种类似系绳的蛋白来促进对小振幅振动的检测，而这些振动对于感知细微的触觉表面是必不可少的。
