Piezo2 is required for Merkel cell mechanotransduction

How we sense touch remains fundamentally unknown(1,2). The Merkel cell-neurite complex is a gentle touch receptor in the skin that mediates slowly-adapting (SA) responses of Aβ sensory fibers to encode fine details of objects(3-6). This mechanoreceptor complex was recognized to play an essential role in sensing gentle touch nearly 50 years ago(3,4). However, whether Merkel cells or afferent fibers themselves sense mechanical force is still debated, and the molecular mechanism of mechanotransduction is unknown(1,2,7-12). Interestingly, synapse-like junctions are observed between Merkel cells and associated afferents(6,13-15), and yet it is unclear if Merkel cells are inherently mechanosensitive or whether they can rapidly transmit such information to the neighboring nerve(1,2,16,17). Here we show for the first time that Merkel cells produce touch-sensitive currents in vitro. Piezo2, a mechanically-activated (MA) cation channel, is expressed in Merkel cells. We engineered mice deficient in Piezo2 in the skin, but not in sensory neurons, and show that Merkel cell mechanosensitivity completely depends on Piezo2. In these mice, Merkel cell-neurite complex-mediated SA responses in vivo show reduced static firing rates, and moreover, they display moderately decreased behavioral responses to gentle touch. Our results indicate that Piezo2 is the Merkel cell mechanotransduction channel and provide the first line of evidence that Piezos play a physiological role in mechanosensation in mammals. Furthermore, our data present evidence for a two-receptor site model, where both Merkel cells and innervating afferents act in concert as mechanosensors. The two-receptor system could provide this mechanoreceptor complex with a tuning mechanism to achieve highly sophisticated responses to a given mechanical stimulus(15,18,19).