Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
Neuron. 2023 Oct 18;111(20):3211-3229.e9. doi: 10.1016/j.neuron.2023.08.023. Epub 2023 Sep 18.
Across mammalian skin, structurally complex and diverse mechanosensory end organs respond to mechanical stimuli and enable our perception of dynamic, light touch. How forces act on morphologically dissimilar mechanosensory end organs of the skin to gate the requisite mechanotransduction channel Piezo2 and excite mechanosensory neurons is not understood. Here, we report high-resolution reconstructions of the hair follicle lanceolate complex, Meissner corpuscle, and Pacinian corpuscle and the subcellular distribution of Piezo2 within them. Across all three end organs, Piezo2 is restricted to the sensory axon membrane, including axon protrusions that extend from the axon body. These protrusions, which are numerous and elaborate extensively within the end organs, tether the axon to resident non-neuronal cells via adherens junctions. These findings support a unified model for dynamic touch in which mechanical stimuli stretch hundreds to thousands of axon protrusions across an end organ, opening proximal, axonal Piezo2 channels and exciting the neuron.
哺乳动物的皮肤中,结构复杂多样的机械感受器终末器官对机械刺激做出反应,使我们能够感知动态的轻触。力如何作用于皮肤形态不同的机械感受器终末器官以门控必需的机械转导通道 Piezo2 并激发机械感觉神经元尚不清楚。在这里,我们报告了毛囊镰状复合体、Meissner 小体和 Pacinian 小体的高分辨率重建,以及它们内部 Piezo2 的亚细胞分布。在所有三个终末器官中,Piezo2 仅限于感觉轴突膜,包括从轴突体延伸出的轴突突起。这些突起在终末器官中数量众多且广泛延伸,通过黏着连接将轴突固定在常驻非神经元细胞上。这些发现支持了一个统一的动态触觉模型,即机械刺激拉伸数百到数千个轴突突起穿过一个终末器官,打开近端的、轴突的 Piezo2 通道并激发神经元。