RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis.

Abstract:

:Gastrointestinal enterochromaffin cells regulate bone and gut homeostasis via serotonin (5-hydroxytryptamine [5-HT]) production. A recent report suggested that gut microbes regulate 5-HT levels; however, the precise underlying molecular mechanisms are unexplored. Here, we reveal that the cation channel Piezo1 in the gut acts as a sensor of single-stranded RNA (ssRNA) governing 5-HT production. Intestinal epithelium-specific deletion of mouse Piezo1 profoundly disturbed gut peristalsis, impeded experimental colitis, and suppressed serum 5-HT levels. Because of systemic 5-HT deficiency, conditional knockout of Piezo1 increased bone formation. Notably, fecal ssRNA was identified as a natural Piezo1 ligand, and ssRNA-stimulated 5-HT synthesis from the gut was evoked in a MyD88/TRIF-independent manner. Colonic infusion of RNase A suppressed gut motility and increased bone mass. These findings suggest gut ssRNA as a master determinant of systemic 5-HT levels, indicating the ssRNA-Piezo1 axis as a potential prophylactic target for treatment of bone and gut disorders.

journal_name

Cell

journal_title

Cell

authors

Sugisawa E,Takayama Y,Takemura N,Kondo T,Hatakeyama S,Kumagai Y,Sunagawa M,Tominaga M,Maruyama K

doi

10.1016/j.cell.2020.06.022

subject

Has Abstract

pub_date

2020-08-06 00:00:00

pages

609-624.e21

issue

3

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(20)30754-6

journal_volume

182

pub_type

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