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

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 re...

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Bibliographic Details
Published in:Cell metabolism 2006-12, Vol.4 (6), p.429-440
Main Authors: Liang, Bin, Moussaif, Mustapha, Kuan, Chih-Jen, Gargus, J. Jay, Sze, Ji Ying
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus - genetics
Animals
Animals, Genetically Modified
Caenorhabditis elegans - genetics
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Cell Nucleus - genetics
Cell Nucleus - metabolism
Fluoxetine - pharmacology
Forkhead Transcription Factors - genetics
Forkhead Transcription Factors - metabolism
HUMDISEASE
Models, Animal
MOLNEURO
Mutation
Neurons - metabolism
Neurosecretory Systems - metabolism
Receptor, IGF Type 1 - genetics
Receptor, IGF Type 1 - immunology
Receptor, Insulin - genetics
Receptor, Insulin - metabolism
Serotonin - genetics
Serotonin - metabolism
Serotonin Uptake Inhibitors - pharmacology
Signal Transduction - drug effects
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary: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.
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2006.11.004