Parallel pathways for serotonin biosynthesis and metabolism in C. elegans.
Nat Chem Biol
; 19(2): 141-150, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36216995
ABSTRACT
The neurotransmitter serotonin plays a central role in animal behavior and physiology, and many of its functions are regulated via evolutionarily conserved biosynthesis and degradation pathways. Here we show that in Caenorhabditis elegans, serotonin is abundantly produced in nonneuronal tissues via phenylalanine hydroxylase, in addition to canonical biosynthesis via tryptophan hydroxylase in neurons. Combining CRISPR-Cas9 genome editing, comparative metabolomics and synthesis, we demonstrate that most serotonin in C. elegans is incorporated into N-acetylserotonin-derived glucosides, which are retained in the worm body and further modified via the carboxylesterase CEST-4. Expression patterns of CEST-4 suggest that serotonin or serotonin derivatives are transported between different tissues. Last, we show that bacterial indole production interacts with serotonin metabolism via CEST-4. Our results reveal a parallel pathway for serotonin biosynthesis in nonneuronal cell types and further indicate that serotonin-derived metabolites may serve distinct signaling functions and contribute to previously described serotonin-dependent phenotypes.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Caenorhabditis elegans
/
Proteínas de Caenorhabditis elegans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos