Sensory Schwann cells set perceptual thresholds for touch and selectively regulate mechanical nociception

Ojeda-Alonso, Julia; Calvo-Enrique, Laura; Paricio-Montesinos, Ricardo; Kumar, Rakesh; Dong-Zhang, Ming; Poulet, James F.A.; Ernfors, Patrik; Lewin, Gary R.

doi:10.1101/2022.02.04.477749

Cited by 5 publications

(14 citation statements)

References 49 publications

(54 reference statements)

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“…Additionally, there is now evidence that sensory neuron mechanosensitivity may not be solely dependent on channels within the sensory cell membrane. Thus, recently identified specialized Schwann cells that surround the peripheral endings of unmyelinated nociceptors may directly participate in the detection of noxious mechanical stimuli ( Abdo et al, 2019 ; Ojeda-Alonso et al, 2022 Preprint ). In addition, cells that form specialized sensory end-organs innervated by mechanoreceptors in birds were also recently shown to be mechanosensitive ( Nikolaev et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Lack of evidence for participation of TMEM150C in sensory mechanotransduction

Ojeda-Alonso

Bégay

Garcia-Contreras

et al. 2022

Journal of General Physiology

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The membrane protein TMEM150C has been proposed to form a mechanosensitive ion channel that is required for normal proprioceptor function. Here, we examined whether expression of TMEM150C in neuroblastoma cells lacking Piezo1 is associated with the appearance of mechanosensitive currents. Using three different modes of mechanical stimuli, indentation, membrane stretch, and substrate deflection, we could not evoke mechanosensitive currents in cells expressing TMEM150C. We next asked if TMEM150C is necessary for the normal mechanosensitivity of cutaneous sensory neurons. We used an available mouse model in which the Tmem150c locus was disrupted through the insertion of a LacZ cassette with a splice acceptor that should lead to transcript truncation. Analysis of these mice indicated that ablation of the Tmem150c gene was not complete in sensory neurons of the dorsal root ganglia (DRG). Using a CRISPR/Cas9 strategy, we made a second mouse model in which a large part of the Tmem150c gene was deleted and established that these Tmem150c−/− mice completely lack TMEM150C protein in the DRGs. We used an ex vivo skin nerve preparation to characterize the mechanosenstivity of mechanoreceptors and nociceptors in the glabrous skin of the Tmem150c−/− mice. We found no quantitative alterations in the physiological properties of any type of cutaneous sensory fiber in Tmem150c−/− mice. Since it has been claimed that TMEM150C is required for normal proprioceptor function, we made a quantitative analysis of locomotion in Tmem150c−/− mice. Here again, we found no indication that there was altered gait in Tmem150c−/− mice compared to wild-type controls. In summary, we conclude that existing mouse models that have been used to investigate TMEM150C function in vivo are problematic. Furthermore, we could find no evidence that TMEM150C forms a mechanosensitive channel or that it is necessary for the normal mechanosensitivity of cutaneous sensory neurons.

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Section: Discussionmentioning

confidence: 99%

Lack of evidence for participation of TMEM150C in sensory mechanotransduction

Ojeda-Alonso

Bégay

Garcia-Contreras

et al. 2022

Journal of General Physiology

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“…Meissner corpuscles endow humans with the remarkable ability to manipulate objects and tools, and enable tactile specialist birds to carry out a multitude of foraging behaviors 5,7,[22][23][24][25] . Whether mammalian LCs are mechanosensitive remains to be determined, but appears likely given that dissociated murine Schwann cells are mechanosensitive in culture 10,11 .…”

Section: Discussionmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

3D architecture and a bi-cellular mechanism of touch detection in mechanosensory corpuscle

Nikolaev

Ziolkowski

Pang

et al. 2023

Preprint

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Mechanosensory corpuscles detect transient touch and vibratory signals in the skin of vertebrates, enabling navigation, foraging, and precise manipulation of objects1. The corpuscle core comprises a terminal neurite of a mechanoreceptor afferent, the only known touch-sensing element within corpuscles, surrounded by terminal Schwann cells called lamellar cells (LCs)2-4. However, the precise corpuscular ultrastructure, and the role of LCs in touch detection are unknown. Here we used enhanced focused ion beam scanning electron microscopy and electron tomography to reveal the three-dimensional architecture of avian Meissner (Grandry) corpuscle5. We show that corpuscles contain a stack of LCs innervated by two afferents, which form large-area contacts with LCs. LCs form tether-like connections with the afferent membrane and contain dense core vesicles which release their content onto the afferent. Furthermore, by performing simultaneous electrophysiological recordings from both cell types, we show that mechanosensitive LCs use calcium influx to trigger action potential firing in the afferent and thus serve as physiological touch sensors in the skin. Our findings suggest a bi-cellular mechanism of touch detection, which comprises the afferent and LCs, likely enables corpuscles to encode the nuances of tactile stimuli.

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“…Although morphologically and functionally diverse, these end organs invariably contain terminal Schwann cells (TSC) that form close interactions with mechanoreceptor afferent terminals. The afferents, which express mechanically gated ion channels such as Piezo2 (4,5), are considered to be the only touch-sensing elements within these end organs, but recent work has revealed that dissociated mouse Schwann cells display mechanosensitivity in culture (6,7). Moreover, mammalian Meissner corpuscles and their avian analogs (historically called corpuscles of Grandry and referred to here as avian Meissner corpuscles) contain TSCs known as lamellar cells (LCs) (8,9), which fire mechanically activated action potentials (APs) in intact avian Meissner corpuscles in situ (10).…”

Section: Introductionmentioning

confidence: 99%

3D architecture and a bicellular mechanism of touch detection in mechanosensory corpuscle

Nikolaev,

Ziolkowski,

Pang

et al. 2023

Sci. Adv.

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Mechanosensory corpuscles detect transient touch and vibration in the skin of vertebrates, enabling precise sensation of the physical environment. The corpuscle contains a mechanoreceptor afferent surrounded by lamellar cells (LCs), but corpuscular ultrastructure and the role of LCs in touch detection are unknown. We report the three-dimensional architecture of the avian Meissner (Grandry) corpuscle acquired using enhanced focused ion beam scanning electron microscopy and machine learning-based segmentation. The corpuscle comprises a stack of LCs interdigitated with terminal endings from two afferents. Simultaneous electrophysiological recordings from both cell types revealed that mechanosensitive LCs use calcium influx to trigger action potentials in the afferent and thus serve as physiological touch sensors in the skin. The elaborate architecture and bicellular sensory mechanism in the corpuscles, which comprises the afferents and LCs, create the capacity for nuanced encoding of the submodalities of touch.

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Sensory Schwann cells set perceptual thresholds for touch and selectively regulate mechanical nociception

Cited by 5 publications

References 49 publications

Lack of evidence for participation of TMEM150C in sensory mechanotransduction

Lack of evidence for participation of TMEM150C in sensory mechanotransduction

3D architecture and a bi-cellular mechanism of touch detection in mechanosensory corpuscle

3D architecture and a bicellular mechanism of touch detection in mechanosensory corpuscle

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