Limits...
Cell-Autonomous Gβ Signaling Defines Neuron-Specific Steady State Serotonin Synthesis in Caenorhabditis elegans.

Xu L, Choi S, Xie Y, Sze JY - PLoS Genet. (2015)

Bottom Line: We found that signaling through cell autonomous GPB-1 to the OCR-2 TRPV channel defines the baseline expression of 5-HT synthesis enzyme tryptophan hydroxylase tph-1 in ADF chemosensory neurons.These results revealed a Gβ-mediated signaling operating in differentiated cells to specify intrinsic functional properties, and indicate that baseline TPH expression is not a default generic serotonergic fate, but is programmed in a cell-specific manner in the mature nervous system.Cell-specific regulation of TPH expression could be a general principle for tailored steady state 5-HT synthesis in functionally distinct neurons and their regulation of innate behavior.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, United States of America.

ABSTRACT
Heterotrimeric G proteins regulate a vast array of cellular functions via specific intracellular effectors. Accumulating pharmacological and biochemical studies implicate Gβ subunits as signaling molecules interacting directly with a wide range of effectors to modulate downstream cellular responses, in addition to their role in regulating Gα subunit activities. However, the native biological roles of Gβ-mediated signaling pathways in vivo have been characterized only in a few cases. Here, we identified a Gβ GPB-1 signaling pathway operating in specific serotonergic neurons to the define steady state serotonin (5-HT) synthesis, through a genetic screen for 5-HT synthesis mutants in Caenorhabditis elegans. We found that signaling through cell autonomous GPB-1 to the OCR-2 TRPV channel defines the baseline expression of 5-HT synthesis enzyme tryptophan hydroxylase tph-1 in ADF chemosensory neurons. This Gβ signaling pathway is not essential for establishing the serotonergic cell fates and is mechanistically separated from stress-induced tph-1 upregulation. We identified that ADF-produced 5-HT controls specific innate rhythmic behaviors. These results revealed a Gβ-mediated signaling operating in differentiated cells to specify intrinsic functional properties, and indicate that baseline TPH expression is not a default generic serotonergic fate, but is programmed in a cell-specific manner in the mature nervous system. Cell-specific regulation of TPH expression could be a general principle for tailored steady state 5-HT synthesis in functionally distinct neurons and their regulation of innate behavior.

No MeSH data available.


ADF-produced 5-HT modulates specific 5-HT-regulated innate behaviors.(A)tph-1 expressed in ADF not in NSM rescued pumping rates of tph-1 mutants. (B)tph-1 expressed in ADF and in NSM concerted to reduce locomotory rates. (C—D) tph-1 expressed in ADF and NSM is not required for 5-HT-regulation of egg-laying rates or egg accumulation in the uterus. Data represent the summary of 4–9 trials. Differences between the groups are indicated, and the differences to WT are marked above the bars, ** p < 0.01, *** p < 0.001 (ANOVA followed by Bonferroni test).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4581872&req=5

pgen.1005540.g007: ADF-produced 5-HT modulates specific 5-HT-regulated innate behaviors.(A)tph-1 expressed in ADF not in NSM rescued pumping rates of tph-1 mutants. (B)tph-1 expressed in ADF and in NSM concerted to reduce locomotory rates. (C—D) tph-1 expressed in ADF and NSM is not required for 5-HT-regulation of egg-laying rates or egg accumulation in the uterus. Data represent the summary of 4–9 trials. Differences between the groups are indicated, and the differences to WT are marked above the bars, ** p < 0.01, *** p < 0.001 (ANOVA followed by Bonferroni test).

Mentions: C. elegans feeds continuously on a E. coli bacterial lawn, by rhythmic contractions of the pharyngeal muscles [33]. The rate of pharyngeal pumping is a measure of C. elegans feeding behavior and is modulated by food availability and 5-HT [33]. Abundant food or applying exogenous 5-HT stimulates the pumping rates. In the presence of food, tph-1 mutants displayed reduced pumping rates compared to WT animals, as previously observed [9]. We observed that the ADF::tph-1 transgene robustly rescued the pumping rate (Fig 7A). In contrast, the NSM::tph-1 transgene did not produce a significant effect (Fig 7A), consistent with the report that laser ablation of NSMs did not reduce the pumping rate [33]. Because ADF senses salts, biotin and nucleotide derivatives [22], ADF-produced 5-HT may modulate the neural circuit that relays attractive signals of nutritious compounds to feeding behavior.


Cell-Autonomous Gβ Signaling Defines Neuron-Specific Steady State Serotonin Synthesis in Caenorhabditis elegans.

Xu L, Choi S, Xie Y, Sze JY - PLoS Genet. (2015)

ADF-produced 5-HT modulates specific 5-HT-regulated innate behaviors.(A)tph-1 expressed in ADF not in NSM rescued pumping rates of tph-1 mutants. (B)tph-1 expressed in ADF and in NSM concerted to reduce locomotory rates. (C—D) tph-1 expressed in ADF and NSM is not required for 5-HT-regulation of egg-laying rates or egg accumulation in the uterus. Data represent the summary of 4–9 trials. Differences between the groups are indicated, and the differences to WT are marked above the bars, ** p < 0.01, *** p < 0.001 (ANOVA followed by Bonferroni test).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581872&req=5

pgen.1005540.g007: ADF-produced 5-HT modulates specific 5-HT-regulated innate behaviors.(A)tph-1 expressed in ADF not in NSM rescued pumping rates of tph-1 mutants. (B)tph-1 expressed in ADF and in NSM concerted to reduce locomotory rates. (C—D) tph-1 expressed in ADF and NSM is not required for 5-HT-regulation of egg-laying rates or egg accumulation in the uterus. Data represent the summary of 4–9 trials. Differences between the groups are indicated, and the differences to WT are marked above the bars, ** p < 0.01, *** p < 0.001 (ANOVA followed by Bonferroni test).
Mentions: C. elegans feeds continuously on a E. coli bacterial lawn, by rhythmic contractions of the pharyngeal muscles [33]. The rate of pharyngeal pumping is a measure of C. elegans feeding behavior and is modulated by food availability and 5-HT [33]. Abundant food or applying exogenous 5-HT stimulates the pumping rates. In the presence of food, tph-1 mutants displayed reduced pumping rates compared to WT animals, as previously observed [9]. We observed that the ADF::tph-1 transgene robustly rescued the pumping rate (Fig 7A). In contrast, the NSM::tph-1 transgene did not produce a significant effect (Fig 7A), consistent with the report that laser ablation of NSMs did not reduce the pumping rate [33]. Because ADF senses salts, biotin and nucleotide derivatives [22], ADF-produced 5-HT may modulate the neural circuit that relays attractive signals of nutritious compounds to feeding behavior.

Bottom Line: We found that signaling through cell autonomous GPB-1 to the OCR-2 TRPV channel defines the baseline expression of 5-HT synthesis enzyme tryptophan hydroxylase tph-1 in ADF chemosensory neurons.These results revealed a Gβ-mediated signaling operating in differentiated cells to specify intrinsic functional properties, and indicate that baseline TPH expression is not a default generic serotonergic fate, but is programmed in a cell-specific manner in the mature nervous system.Cell-specific regulation of TPH expression could be a general principle for tailored steady state 5-HT synthesis in functionally distinct neurons and their regulation of innate behavior.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, United States of America.

ABSTRACT
Heterotrimeric G proteins regulate a vast array of cellular functions via specific intracellular effectors. Accumulating pharmacological and biochemical studies implicate Gβ subunits as signaling molecules interacting directly with a wide range of effectors to modulate downstream cellular responses, in addition to their role in regulating Gα subunit activities. However, the native biological roles of Gβ-mediated signaling pathways in vivo have been characterized only in a few cases. Here, we identified a Gβ GPB-1 signaling pathway operating in specific serotonergic neurons to the define steady state serotonin (5-HT) synthesis, through a genetic screen for 5-HT synthesis mutants in Caenorhabditis elegans. We found that signaling through cell autonomous GPB-1 to the OCR-2 TRPV channel defines the baseline expression of 5-HT synthesis enzyme tryptophan hydroxylase tph-1 in ADF chemosensory neurons. This Gβ signaling pathway is not essential for establishing the serotonergic cell fates and is mechanistically separated from stress-induced tph-1 upregulation. We identified that ADF-produced 5-HT controls specific innate rhythmic behaviors. These results revealed a Gβ-mediated signaling operating in differentiated cells to specify intrinsic functional properties, and indicate that baseline TPH expression is not a default generic serotonergic fate, but is programmed in a cell-specific manner in the mature nervous system. Cell-specific regulation of TPH expression could be a general principle for tailored steady state 5-HT synthesis in functionally distinct neurons and their regulation of innate behavior.

No MeSH data available.