RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis | Zendy

Erika Sugisawa | Zendy; Yasunori Takayama | Zendy; Naoki Takemura | Zendy; Takeshi Kondo | Zendy; Shigetsugu Hatakeyama | Zendy; Yutaro Kumagai | Zendy; Masataka Sunagawa | Zendy; Makoto Tominaga | Zendy; Kenta Maruyama | Zendy

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RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis

Author(s) -

Erika Sugisawa,

Yasunori Takayama,

Naoki Takemura,

Takeshi Kondo,

Shigetsugu Hatakeyama,

Yutaro Kumagai,

Masataka Sunagawa,

Makoto Tominaga,

Kenta Maruyama

Publication year - 2020

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2020.06.022

Subject(s) - piezo1 , enterochromaffin cell , biology , serotonin , conditional gene knockout , rnase p , gut flora , microbiology and biotechnology , rna , immunology , genetics , gene , ion channel , receptor , phenotype , mechanosensitive channels

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.

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