Serotonin targets the DAF-16/FOXO signaling pathway to modulate stress responses

Bin Liang, Mustapha Moussaif, Chih Jen Kuan, J. Jay Gargus, Ji Ying Sze

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Stress response is a fundamental form of behavioral and physiological plasticity. Here we describe how serotonin (5HT) governs stress behavior by regulating DAF-2 insulin/IGF-1 receptor signaling to the DAF-16/FOXO transcription factor at the nexus of development, metabolism, immunity, and stress responses in C. elegans. Serotonin-deficient tph-1 mutants, like daf-2 mutants, exhibit DAF-16 nuclear accumulation and constitutive physiological stress states. Exogenous 5HT and fluoxetine (Prozac) prevented DAF-16 nuclear accumulation in wild-type animals under stresses. Genetic analyses imply that DAF-2 is a downstream target of 5HT signaling and that distinct serotonergic neurons act through distinct 5HT receptors to influence distinct DAF-16-mediated stress responses. We suggest that modulation of FOXO by 5HT represents an ancient feature of stress physiology and that the C. elegans is a genetically tractable model that can be used to delineate the molecular mechanisms and drug actions linking 5HT, neuroendocrine signaling, immunity, and mitochondrial function.

Original languageEnglish (US)
Pages (from-to)429-440
Number of pages12
JournalCell metabolism
Volume4
Issue number6
DOIs
StatePublished - Dec 1 2006
Externally publishedYes

Keywords

  • HUMDISEASE
  • MOLNEURO

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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