Piezo proteins: incidence and abundance in the enteric nervous system. Is there a link with mechanosensitivity?

Mazzuoli‐Weber, Gemma; Kugler, Eva Maria; Bühler, Carina Ines; Kreutz, Florian; Demir, Ihsan Ekin; Ceyhan, Onur Güralp; Zeller, Florian; Schemann, Michael

doi:10.1007/s00441-018-2926-7

Cited by 21 publications

(27 citation statements)

References 44 publications

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“…PIEZO1 encodes a recently described mechanosensitive cation channel [15] with several biological functions including human T cell activation [52], direction of lineage choice in human neural stem cells [71], and mediating the age-related loss of function of oligodendrocyte progenitor cells [79]. PIEZO1 is expressed in the neurons of the human substantia nigra [20,76] and also is ubiquitously expressed in human enteric neurons [58], both neuronal types impacted by PD [10,43]. Interestingly, the expression of PIEZO2 -PIEZO1's paralogis regulated by, putatively melanocyte-derived, dopamine signaling in mouse primary sensory neurons [69] but whether this regulation is relevant for PIEZO1 is currently unknown.…”

Section: Figure Andmentioning

confidence: 99%

“…Law MH 1* , Bishop DT 2* , Lee JE 3# , Brossard M 4,5# , Martin NG 6 , Moses EK 7 , Song F 8 , Barrett JH 2 , Kumar R 9 , Easton DF 10 , Pharoah PD 11 , Swerdlow AJ 12,13 , Kypreou KP 14 , Taylor JC 2 , Harland M 2 , Randerson-Moor J 2 , Akslen LA 15,16 , Andresen PA 17 , Avril MF 18 , Azizi E 19,20 , Scarrà GB 21,22 , Brown KM 23 , Dȩbniak T 24 , Duffy DL 6 , Elder DE 25 , Fang S 3 , Friedman E 20 , Galan P 26 , Ghiorzo P 21,22 , Gillanders EM 27 , Goldstein AM 23 , Gruis NA 28 35,37 , Mann GJ 38 , Molven A 16,39 , Montgomery GW 40 , Novaković S 41 , Olsson H 42,43 , Puig S 44,45 , Puig-Butille JA 44,45 , Wu W 46,47 , , Qureshi AA 48 , Radford-Smith GL 49,50,51 , van der Stoep N 52 , van Doorn R 28 , Whiteman DC 53 , Craig JE 54 , Schadendorf D 55,56 , Simms LA 47 , Burdon KP 57 , Nyholt DR 40,58 , Pooley KA 10 , Orr N 59 , Stratigos AJ 14 , Cust AE 60 , Ward SV 7 , Hayward NK 61 , Han J 46,47 , Schulze HJ…”

Section: List Of Members Of the Melanoma Meta-analysis Consortiummentioning

confidence: 99%

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Overlapping genetic architecture between Parkinson disease and melanoma

et al. 2019

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Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these diseases can support epidemiologic findings and identify common risk genes and biological pathways. Here we apply polygenic, linkage disequilibrium-informed methods to the largest available case-control, genome-wide association study summary statistic data for melanoma and PD. We identify positive and significant genetic correlation (correlation: 0.17, 95% CI 0.10 to 0.24; P = 4.09 × 10-06) between melanoma and PD. We further demonstrate melanoma and PD-inferred gene expression to overlap across tissues (correlation: 0.14, 95% CI 0.06 to 0.22; P = 7.87 × 10-04), and highlight seven genes including PIEZO1, TRAPPC2L, and SOX6 as potential mediators of the genetic correlation between melanoma and PD. These findings demonstrate specific, shared genetic architecture between PD and melanoma that manifests at the level of gene expression.

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Section: Figure Andmentioning

confidence: 99%

Section: List Of Members Of the Melanoma Meta-analysis Consortiummentioning

confidence: 99%

Overlapping genetic architecture between Parkinson disease and melanoma

et al. 2019

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“…5b), suggesting they have the capacity to directly sense distention. Previous studies reported Piezo1 expression in the ENS (78,79), which our atlas allows us to map to specific subsets. This refinement raises the hypothesis that peristalsis is at least partially driven by distention, specifically via motor neuron depolarization through Piezo1.…”

Section: Motor Neuron Expression Profiles Suggest That Mechanosensatimentioning

confidence: 84%

The enteric nervous system of the human and mouse colon at a single-cell resolution

Drokhlyansky

Smillie

Wittenberghe

et al. 2019

Preprint

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As the largest branch of the autonomic nervous system, the enteric nervous system (ENS) controls the entire gastrointestinal tract, but remains incompletely characterized. Here, we develop RAISIN RNA-seq, which enables the capture of intact single nuclei along with ribosome-bound mRNA, and use it to profile the adult mouse and human colon to generate a reference map of the ENS at a single-cell resolution. This map reveals an extraordinary diversity of neuron subsets across intestinal locations, ages, and circadian phases, with conserved transcriptional programs that are shared between human and mouse. These data suggest possible revisions to the current model of peristalsis and molecular mechanisms that may allow enteric neurons to orchestrate tissue homeostasis, including immune regulation and stem cell maintenance. Human enteric neurons specifically express risk genes for neuropathic, inflammatory, and extra-intestinal diseases with concomitant gut dysmotility. Our study therefore provides a roadmap to understanding the ENS in health and disease.

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“…Functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG) would not be an option due to capsule ferromagnetic components, though as previously mentioned, one MEG study detailed evidence of midline parieto-occipital activity linked to stomach input under resting conditions (30) Answering these questions would likely require the application of invasive (i.e., nonhuman) studies capable of evaluating mechanotransducers at molecular levels. One candidate would be PIEZO channels (13,14), which are heavily expressed in the stomach (51,52) -though many other mechanical (e.g., transient receptor potential (TRP) channels) and voltage-gated ion channels are possibilities (either individually or in combination). At the cellular level, several types of mechanosensitive neurons within the enteric nervous system are known to play a role in transmitting tensile and mechanical forces, including extrinsic vagal afferent nerve endings in the upper gut and Dogiel type II neurons (spinal afferent nerve endings, which predominantly innervate the lower gut might be considered less likely) (53).…”

Section: Discussionmentioning

confidence: 99%

Neural indicators of human gut feelings

Mayeli

et al. 2021

Preprint

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Understanding the neural processes that govern the human gut-brain connection has been challenging due to the inaccessibility of the body′s interior. In this study, we aimed to identify neural responses to gastrointestinal sensation (i.e., the neural basis of ′gut feelings′) in healthy humans using a minimally invasive mechanosensory probe. Combining electroencephalography and electrogastrography with signal detection theory measures, we quantified brain, stomach, and perceptual (button-press) responses following the ingestion of a vibrating capsule. The relationship between vibration strength and perceptual sensitivity was evaluated using two stimulation conditions (normal and enhanced). Most individuals successfully perceived capsule stimulation in both conditions, as evidenced by above chance accuracy scores. Perceptual accuracy improved significantly during the enhanced relative to normal stimulation, which was associated with faster reaction time and reduced reaction time variability. Stomach stimulation induced responses in a cluster of parieto-occipital leads near the midline via a late positive potential emerging 300-600 milliseconds after stimulation onset. Moreover, these ′gastric evoked potentials′ showed dose-dependent increases in amplitude and were significantly correlated with perceptual accuracy. Our findings are consistent with recent neurogastric and optogenetic studies demonstrating a role for posteromedial cortices in gastrointestinal interoception and body dissociation and highlight a unique form of enterically-focused sensory monitoring within the human brain. Overall, these results show that this minimally invasive approach could serve as a useful tool for understanding gut-brain interactions in healthy and clinical populations.

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Piezo proteins: incidence and abundance in the enteric nervous system. Is there a link with mechanosensitivity?

Cited by 21 publications

References 44 publications

Overlapping genetic architecture between Parkinson disease and melanoma

Overlapping genetic architecture between Parkinson disease and melanoma

The enteric nervous system of the human and mouse colon at a single-cell resolution

Neural indicators of human gut feelings

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