RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis
In: Cell, Jg. 182 (2020-08-01), S. 609-609
Online
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Zugriff:
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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RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis
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Autor/in / Beteiligte Person: | Kumagai, Yutaro ; Sugisawa, Erika ; Takayama, Yasunori ; Tominaga, Makoto ; Takemura, Naoki ; Sunagawa, Masataka ; Maruyama, Kenta ; Hatakeyama, Shigetsugu ; Kondo, Takeshi |
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Zeitschrift: | Cell, Jg. 182 (2020-08-01), S. 609-609 |
Veröffentlichung: | Elsevier BV, 2020 |
Medientyp: | unknown |
ISSN: | 0092-8674 (print) |
DOI: | 10.1016/j.cell.2020.06.022 |
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