Document Detail


Serotonin targets the DAF-16/FOXO signaling pathway to modulate stress responses.
MedLine Citation:
PMID:  17141627     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Bin Liang; Mustapha Moussaif; Chih-Jen Kuan; J Jay Gargus; Ji Ying Sze
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cell metabolism     Volume:  4     ISSN:  1550-4131     ISO Abbreviation:  Cell Metab.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-04     Completed Date:  2007-02-02     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  429-40     Citation Subset:  IM    
Affiliation:
Department of Anatomy & Neurobiology, School of Medicine, University of California, Irvine, Irvine, California 92697, USA.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus / genetics
Animals
Animals, Genetically Modified
Caenorhabditis elegans / genetics,  metabolism*
Caenorhabditis elegans Proteins / genetics,  metabolism*
Cell Nucleus / genetics,  metabolism
Fluoxetine / pharmacology
Forkhead Transcription Factors / genetics,  metabolism
Models, Animal
Mutation
Neurons / metabolism*
Neurosecretory Systems / metabolism
Receptor, IGF Type 1 / genetics,  immunology
Receptor, Insulin / genetics,  metabolism
Serotonin / genetics,  metabolism*
Serotonin Uptake Inhibitors / pharmacology
Signal Transduction* / drug effects
Transcription Factors / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Caenorhabditis elegans Proteins; 0/DAF-2 protein, C elegans; 0/Forkhead Transcription Factors; 0/Serotonin Uptake Inhibitors; 0/Transcription Factors; 0/daf-16 protein, C elegans; 50-67-9/Serotonin; 54910-89-3/Fluoxetine; EC 2.7.10.1/Receptor, IGF Type 1; EC 2.7.10.1/Receptor, Insulin
Comments/Corrections
Comment In:
Cell Metab. 2006 Dec;4(6):415-7   [PMID:  17141622 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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