Document Detail


A neuronal signaling pathway of CaMKII and Gqα regulates experience-dependent transcription of tph-1.
MedLine Citation:
PMID:  23325232     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dynamic serotonin biosynthesis is important for serotonin function; however, the mechanisms that underlie experience-dependent transcriptional regulation of the rate-limiting serotonin biosynthetic enzyme tryptophan hydroxylase (TPH) are poorly understood. Here, we characterize the molecular and cellular mechanisms that regulate increased transcription of Caenorhabditis elegans tph-1 in a pair of serotonergic neurons ADF during an aversive experience with pathogenic bacteria, a common environmental peril for worms. Training with pathogenic bacteria induces a learned aversion to the smell of the pathogen, a behavioral plasticity that depends on the serotonin signal from ADF neurons. We demonstrate that pathogen training increases ADF neuronal activity. While activating ADF increases tph-1 transcription, inhibiting ADF activity abolishes the training effect on tph-1, demonstrating the dependence of tph-1 transcriptional regulation on ADF neural activity. At the molecular level, the C. elegans homolog of CaMKII, UNC-43, functions cell-autonomously in ADF neurons to generate training-dependent enhancement in neuronal activity and tph-1 transcription, and this cell-autonomous function of UNC-43 is required for learning. Furthermore, selective expression of an activated form of UNC-43 in ADF neurons is sufficient to increase ADF activity and tph-1 transcription, mimicking the training effect. Upstream of ADF, the Gqα protein EGL-30 facilitates training-dependent induction of tph-1 by functional regulation of olfactory sensory neurons, which underscores the importance of sensory experience. Together, our work elucidates the molecular and cellular mechanisms whereby experience modulates tph-1 transcription.
Authors:
Yuqi Qin; Xiaodong Zhang; Yun Zhang
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  33     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-04-01     Revised Date:  2013-07-18    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  925-35     Citation Subset:  IM    
Affiliation:
Department of Organismic and Evolutionary Biology, Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Avoidance Learning / physiology
Behavior, Animal / physiology
Caenorhabditis elegans
Caenorhabditis elegans Proteins / genetics*,  metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics*,  metabolism
GTP-Binding Protein alpha Subunits, Gq-G11 / genetics*,  metabolism
Gene Expression Regulation
Neurons / metabolism*
Phosphorylation
Serotonin / biosynthesis
Signal Transduction / physiology*
Transcription, Genetic
Tryptophan Hydroxylase / genetics*,  metabolism
Grant Support
ID/Acronym/Agency:
P40 OD010440/OD/NIH HHS; R01 DC009852/DC/NIDCD NIH HHS; R01 DC009852/DC/NIDCD NIH HHS
Chemical
Reg. No./Substance:
0/Caenorhabditis elegans Proteins; 0/Egl-30 protein, C elegans; 50-67-9/Serotonin; EC 1.14.16.4/Tryptophan Hydroxylase; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2; EC 2.7.11.17/unc-43 protein, C elegans; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gq-G11
Comments/Corrections

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