Division of Gastroenterology, Department of Medicine
Cell Biology | Cells | Cellular and Molecular Physiology | Digestive System | Fluids and Secretions | Gastroenterology | Molecular Biology
Enterochromaffin (EC) cells constitute the largest population of intestinal epithelial enteroendocrine (EE) cells. EC cells are proposed to be specialized mechanosensory cells that release serotonin in response to epithelial forces, and thereby regulate intestinal fluid secretion. However, it is unknown whether EE and EC cells are directly mechanosensitive, and if so, what the molecular mechanism of their mechanosensitivity is. Consequently, the role of EE and EC cells in gastrointestinal mechanobiology is unclear. Piezo2 mechanosensitive ion channels are important for some specialized epithelial mechanosensors, and they are expressed in mouse and human EC cells. Here, we use EC and EE cell lineage tracing in multiple mouse models to show that Piezo2 is expressed in a subset of murine EE and EC cells, and it is distributed near serotonin vesicles by superresolution microscopy. Mechanical stimulation of a subset of isolated EE cells leads to a rapid inward ionic current, which is diminished by Piezo2 knockdown and channel inhibitors. In these mechanosensitive EE cells force leads to Piezo2-dependent intracellular Ca(2+) increase in isolated cells as well as in EE cells within intestinal organoids, and Piezo2-dependent mechanosensitive serotonin release in EC cells. Conditional knockout of intestinal epithelial Piezo2 results in a significant decrease in mechanically stimulated epithelial secretion. This study shows that a subset of primary EE and EC cells is mechanosensitive, uncovers Piezo2 as their primary mechanotransducer, defines the molecular mechanism of their mechanotransduction and mechanosensitive serotonin release, and establishes the role of epithelial Piezo2 mechanosensitive ion channels in regulation of intestinal physiology.
enterochromaffin cell, gastrointestinal, ion channel, mechanosensitivity, serotonin
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Copyright © 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
DOI of Published Version
Proc Natl Acad Sci U S A. 2018 Aug 7;115(32):E7632-E7641. doi: 10.1073/pnas.1804938115. Epub 2018 Jul 23. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Alcaino, Constanza; Knutson, Kaitlyn R.; Treichel, Anthony J.; Yildiz, Gulcan; Strege, Peter R.; Linden, David R.; Li, Joyce H.; Leiter, Andrew B.; Szurszewski, Joseph H.; Farrugia, Gianrico; and Beyder, Arthur, "A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release" (2018). Open Access Articles. 3534.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.