<i>piezo2b</i>Regulates Vertebrate Light Touch Response

Faucherre, Adèle; Nargeot, Joël; Mangoni, Matteo E.; Jopling, Chris

doi:10.1523/jneurosci.0522-13.2013

Cited by 71 publications

(55 citation statements)

References 25 publications

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“…Interestingly, Drosophila Piezo is required for mechanical nociception, and not for gentle touch sensation 29 . Regardless, our findings highlight the role of Piezos as evolutionarily conserved MA ion channels involved in somatosensory mechanotransduction from flies to mammals 29,30 .…”

mentioning

confidence: 67%

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

Ranade

Woo

Dubin

et al. 2014

Nature

736

819

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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.

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mentioning

confidence: 67%

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

Ranade

Woo

Dubin

et al. 2014

Nature

736

819

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“…Weak β-gal activity was initially detected at E9 (Fig. S2B), when regular heartbeats and blood flow are first established (29). Between E9 and E10.5, β-gal activity increased and was restricted to the developing cardiovascular system, in particular to the vascular endothelium and the inner endocardium surrounding the heart lumen ( Fig.…”

Section: Piezo1mentioning

confidence: 97%

“…We investigated where Piezo1 is expressed at this time. Piezo1 in situ hybridization probes, an antibody that we had previously generated, as well as commercially available antibodies were not sensitive enough to detect expression of endogenous Piezo1 (18,29). We therefore used the Piezo1 promoter-driven β-gal and PLAP reporter genes to analyze the expression pattern of Piezo1.…”

Section: Piezo1mentioning

confidence: 99%

Piezo1, a mechanically activated ion channel, is required for vascular development in mice

Ranade

Qiu

Woo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

707

716

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Mechanosensation is perhaps the last sensory modality not understood at the molecular level. Ion channels that sense mechanical force are postulated to play critical roles in a variety of biological processes including sensing touch/pain (somatosensation), sound (hearing), and shear stress (cardiovascular physiology); however, the identity of these ion channels has remained elusive. We previously identified Piezo1 and Piezo2 as mechanically activated cation channels that are expressed in many mechanosensitive cell types. Here, we show that Piezo1 is expressed in endothelial cells of developing blood vessels in mice. Piezo1-deficient embryos die at midgestation with defects in vascular remodeling, a process critically influenced by blood flow. We demonstrate that Piezo1 is activated by shear stress, the major type of mechanical force experienced by endothelial cells in response to blood flow. Furthermore, loss of Piezo1 in endothelial cells leads to deficits in stress fiber and cellular orientation in response to shear stress, linking Piezo1 mechanotransduction to regulation of cell morphology. These findings highlight an essential role of mammalian Piezo1 in vascular development during embryonic development.

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“…PIEZO1 can be inhibited by a general blocker of mechanosensitive channels, GsMTx4 (Bae et al, 2011), and is shown to be sensitive to ruthenium red (Coste et al, 2010; Coste et al, 2012). Piezo channels are involved in several physiological processes, such as maintaining normal cell density in zebrafish and mammalian epithelial tissue (Eisenhoffer et al, 2012), mediating mechanical nociception in Drosophila larvae (Kim et al, 2012), and light touch in Rohon-Beard neurons in zebrafish (Faucherre et al, 2013). In humans, point mutations in PIEZO1 have been identified in patients suffering from Dehydrated Hereditary Stomatocytosis (DHS), an autosomal dominant hemolytic anemia disease (Zarychanski et al, 2012; Albuisson et al, 2013; Andolfo et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

The Structure of a Conserved Piezo Channel Domain Reveals a Topologically Distinct β Sandwich Fold

et al. 2014

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Summary Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a novel beta sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in Dehydrated Hereditary Stomatocytosis (DHS) patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels.

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piezo2bRegulates Vertebrate Light Touch Response

Cited by 71 publications

References 25 publications

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

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

Piezo1, a mechanically activated ion channel, is required for vascular development in mice

The Structure of a Conserved Piezo Channel Domain Reveals a Topologically Distinct β Sandwich Fold

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