Abstract
Proprioception, the perception of body and limb position, is mediated by proprioceptors, specialized mechanosensory neurons that convey information about the stretch and tension experienced by muscles, tendons, skin, and joints. In mammals, the molecular identity of the stretch-sensitive channel that mediates proprioception is unknown. Here we show that the mechanically activated (MA) nonselective cation channel Piezo2 is expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs in mice. Two independent mouse lines that lack Piezo2 in proprioceptive neurons show severely uncoordinated body movements and abnormal limb positions. Moreover, the mechanosensitivity of Pvalb+ neurons that predominantly mark proprioceptors are dependent on Piezo2 in vitro, and the stretch-induced firing of proprioceptors in muscle-nerve recordings is dramatically reduced in Piezo2-deficient mice. Together, our results indicate that Piezo2 is the major mechanotransducer of mammalian proprioceptors.
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