New Findings What is the central question of this study? Proprioception is initiated by mechanosensitive neurons. However, the identities of the molecular players that mediate proprioceptive sensing are largely unknown. Here, we aimed to identify potential mechanosensitive ion channels that mediate proprioceptive signalling. What is the main finding and its importance? We identify the mechanosensitive ion channel ASIC2 as a key component in proprioceptive sensing and a regulator of spine alignment. AbstractBy 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.
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