Piezo2 is the major transducer of mechanical forces for touch sensation in mice

Abstract

Summary The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals1. It is postulated that mechanically activated (MA) cation channels initiate touch sensation, but the identity of these molecules in mammals has been elusive2. Piezo2 is a rapidly adapting (RA) MA ion channel expressed in a subset of sensory neurons of the dorsal root ganglion (DRG) and in cutaneous mechanoreceptors known as Merkel cell-neurite complexes3,4. Merkel cells have been demonstrated to play a role in vertebrate mechanosensation using Piezo2, particularly in shaping the type of current sent by its innervating sensory neuron4-6. However, major aspects of touch sensation remain intact without Merkel cell activity4,7. Here, we show that mice lacking Piezo2 in both adult sensory neurons and Merkel cells exhibit a profound loss of touch sensation. We precisely localize Piezo2 to the peripheral endings of a broad range of low threshold mechanoreceptors (LTMRs) that innervate both hairy and glabrous skin. Most RA MA currents in DRG neuronal cultures are absent in Piezo2CKO mice, and ex vivo skin nerve preparation studies show that mechanosensitivity of LTMRs strongly depends on Piezo2. This striking cellular phenotype correlates with an unprecedented behavioral phenotype: an almost complete deficit in light touch sensation in multiple behavioral assays, without affecting other somatosensory functions. Our results highlight that a single ion channel that displays RA MA currents in vitro is responsible for the mechanosensitivity of most LTMR subtypes involved in innocuous touch sensation. Interestingly, we find that touch and pain sensation are separable, suggesting that yet-unknown MA ion channel(s) must account for noxious (painful) mechanosensation.

Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

“…C3 expresses Th, Fam19a4, Cpne6 and Piezo2 [50]. Our finding indicates that C9 neurons are Aβ-MNs, consistent with the early idea regarding Aβ-fiber nociceptive DRG neurons [51].…”

TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing

“…Many of these functions require mechanotransduction at the micro-to millisecond scale, suggesting that the transducers are mechanosensitive ion channels (MSCs). This is confirmed by the recent discovery of genes responsible for our senses or touch (Ranade et al, 2014b), hearing (Pan et al, 2013), and proprioception (Boyer et al, 2011;Woo et al, 2015). Yet the genes responsible for our most unwanted experience of mechanotransduction, our sense of pain, remain elusive.…”

“…The latter has been associated with expression of Piezo2 (Ranade et al, 2014b;Woo et al, 2015). To determine whether TACAN is responsible for the ultra-slow adapting current in nociceptors, we recorded whole-cell mechanically-evoked currents from DRG neurons obtained from wild-type mice, transfected with the same set of Alexa488-labeled siRNA molecules.…”

Regulation of Piezo2 Mechanotransduction by Static Plasma Membrane Tension in Primary Afferent Neurons

“…Piezo2 channels are also expressed on Merkel cells of hair follicles and touch domes of the skin, where they are key molecules for the transduction of gentle touch (8 -10). The role of Piezo2 channels in animal behavioral responses to mechanical stimuli has recently been demonstrated using Piezo2 knock-out mice (11).…”