Journal Article

Piezo2 is required for Merkel-cell mechanotransduction

Baba, Yoshichika, Miyamoto, Takashi, Patapoutian, Ardem, Ranade, Sanjeev, Woo, Seung-Hyun, Stucky, Cheryl L., Petrus, Matt, Lumpkin, Ellen A., Qiu, Zhaozhu, Reddy, Kritika, Weyer, Andy D., Dubin, Adrienne E.

2014

Overview

A mouse study shows that non-neuronal epidermal Merkel cells aid fine-touch perception in the skin through their expression of the Piezo2 mechanosensitive cation channel which then actively tunes the response to touch in adjacent somatosensory neurons. Non-neural Merkel cells stay in touch Merkel cells (also known as Merkel-Ranvier cells) are found in the vertebrate epidermis. They are non-neuronal but may make 'synapse-like' contact with neighbouring cells. It has been suggested that they are associated with the sensation of touch, but this has been difficult to prove and remains controversial. In this week's Nature two teams present clear evidence that Merkel cells are autonomous mechanosensors essential to fine touch perception. The cells express the mechanosensitive channel Piezo2, which allows them to actively tune somatosensory neurons' responses to touch. These results are consistent with a compound receptor system model in which epidermal cells help neurons to discriminate between different types of touch — such as flutter, stretch and pressure — and therefore to decode the fine details of objects. 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 responses of Aβ sensory fibres to encode fine details of objects 3 , 4 , 5 , 6 . This mechanoreceptor complex was recognized to have an essential role in sensing gentle touch nearly 50 years ago 3 , 4 . However, whether Merkel cells or afferent fibres themselves sense mechanical force is still debated, and the molecular mechanism of mechanotransduction is unknown 1 , 2 , 7 , 8 , 9 , 10 , 11 , 12 . Synapse-like junctions are observed between Merkel cells and associated afferents 6 , 13 , 14 , 15 , and yet it is unclear whether Merkel cells are inherently mechanosensitive or whether they can rapidly transmit such information to the neighbouring nerve 1 , 2 , 16 , 17 . Here we show that Merkel cells produce touch-sensitive currents in vitro . Piezo2, a mechanically activated 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, slowly adapting responses in vivo mediated by the Merkel cell–neurite complex show reduced static firing rates, and moreover, the mice display moderately decreased behavioural responses to gentle touch. Our results indicate that Piezo2 is the Merkel-cell mechanotransduction channel and provide the first line of evidence that Piezo channels have a physiological role in mechanosensation in mammals. Furthermore, our data present evidence for a two-receptor-site model, in which both Merkel cells and innervating afferents act together 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 .

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 13/31 / 14/19 / 38/1 / 38/77 / 38/90 / 631/378/2620/2621 / 64/60 / 82/80 / 9/74 / Action Potentials / Animals / Cellular signal transduction / Electric Conductivity / Female / Green fluorescent protein / Humanities and Social Sciences / In Vitro Techniques / Ion channels / Ion Channels - deficiency / Ion Channels - genetics / Ion Channels - metabolism / letter / Male / Mechanical properties / Mechanotransduction, Cellular - genetics / Merkel cells / Merkel Cells - metabolism / Mice / Mice, Knockout / multidisciplinary / Neurites - metabolism / Neurons, Afferent - metabolism / Physiological aspects / Physiological research / Science / Skin / Skin - cytology / Skin - innervation / Touch - genetics / Touch - physiology