PIEZO2 in Somatosensory Neurons Controls Gastrointestinal Transit

Authors

M Rocio Servin-Vences
Ruby M Lam
Alize Koolen
Yu Wang
Dimah N Saade
Meaghan Loud
Halil Kacmaz
Suzanne Frausto
Yunxiao Zhang
Arthur Beyder
Kara L Marshall
Carsten G Bönnemann
Alexander T Chesler
Ardem Patapoutian

Publication Date

8-3-2023

Journal

Cell

DOI

10.1016/j.cell.2023.07.006

PMID

37541196

PMCID

PMC10501318

PubMedCentral® Posted Date

8-3-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Humans, Mice, Digestion, Gastrointestinal Transit, Ion Channels, Mechanotransduction, Cellular, Neurons, PIEZO2 deficiency, Piezo2, dorsal root ganglia, gastrointestinal tract, gut motility, gut transit, interoception, mechanosensation, sensory neurons, spinal innervation

Abstract

The gastrointestinal tract is in a state of constant motion. These movements are tightly regulated by the presence of food and help digestion by mechanically breaking down and propelling gut content. Mechanical sensing in the gut is thought to be essential for regulating motility; however, the identity of the neuronal populations, the molecules involved, and the functional consequences of this sensation are unknown. Here, we show that humans lacking PIEZO2 exhibit impaired bowel sensation and motility. Piezo2 in mouse dorsal root, but not nodose ganglia is required to sense gut content, and this activity slows down food transit rates in the stomach, small intestine, and colon. Indeed, Piezo2 is directly required to detect colon distension in vivo. Our study unveils the mechanosensory mechanisms that regulate the transit of luminal contents throughout the gut, which is a critical process to ensure proper digestion, nutrient absorption, and waste removal.