Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-University, Planegg-Martinsried, Germany.
Exp Physiol. 2024 Jan;109(1):135-147. doi: 10.1113/EP090776. Epub 2023 Mar 23.
By translating mechanical forces into molecular signals, proprioceptive neurons provide the CNS with information on muscle length and tension, which is necessary to control posture and movement. However, the identities of the molecular players that mediate proprioceptive sensing are largely unknown. Here, we confirm the expression of the mechanosensitive ion channel ASIC2 in proprioceptive sensory neurons. By combining in vivo proprioception-related functional tests with ex vivo electrophysiological analyses of muscle spindles, we showed that mice lacking Asic2 display impairments in muscle spindle responses to stretch and motor coordination tasks. Finally, analysis of skeletons of Asic2 loss-of-function mice revealed a specific effect on spinal alignment. Overall, we identify ASIC2 as a key component in proprioceptive sensing and a regulator of spine alignment.
通过将机械力转化为分子信号,本体感受神经元为中枢神经系统提供有关肌肉长度和张力的信息,这对于控制姿势和运动是必要的。然而,介导本体感受感知的分子参与者的身份在很大程度上是未知的。在这里,我们证实了机械敏感离子通道 ASIC2 在本体感受感觉神经元中的表达。通过将与体内本体感受相关的功能测试与肌肉梭内的体外电生理分析相结合,我们表明缺乏 Asic2 的小鼠在肌肉梭内对拉伸和运动协调任务的反应中存在缺陷。最后,对 ASIC2 功能丧失型小鼠骨骼的分析显示出对脊柱排列的特定影响。总的来说,我们将 ASIC2 鉴定为本体感受感知的关键组成部分和脊柱排列的调节剂。