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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.


Related in: MedlinePlus

Baseline and pathogen-induced ADF tph-1::gfp expression involve separated GPB-1 functions.(A) Transgenic expressing gpb-1 cDNA in all neurons rescued both baseline and pathogen PA14-induced ADF tph-1::gfp expression in yz71 mutants. (B) Expressing gpb-1 cDNA specifically in ADF restored baseline tph-1::gfp but not the response to PA14. ADF is the only neuronal type expressed in common by the three transgenes that selectively rescued the baseline ADF tph-1::gfp (the ADF and ADL expression was driven by a lin-11 promoter, and the ADF + others expression was driven by the cat-1 promoter). The transgenes expressed in additional amphid neurons including ADF rescued both the baseline and PA14-induced tph-1::gfp expression, but the transgenes that are not expressed in ADF failed to rescue under either condition. For each assay, the value of ADF GFP fluorescence in WT animals fed PA14 and that of mutants and transgenic animals is normalized to the value of WT animals under optimal conditions. Data represent the average of ≥ 2 trials ± SEM. The differences between yz71 mutants and the transgenic animals under optimal growth conditions are marked on the top of white bars, and the differences between the same strains fed OP50 and PA14 are indicated, ** p < 0.01, *** p < 0.001, ANOVA followed by Tukey tests. (C) Model for GPB-1 regulation of the baseline and pathogen-induced tph-1 expression in ADF. Cell-autonomous GPB-1 is necessary and sufficient for the baseline tph-1 expression. GPB-1 regulates PA14-induced tph-1 upregulation by controlling Gqα EGL-30, which acts in AWB and AWC neurons in the pathogen-induced signaling pathway [25], and other Gα signaling in additional amphid neurons.
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pgen.1005540.g004: Baseline and pathogen-induced ADF tph-1::gfp expression involve separated GPB-1 functions.(A) Transgenic expressing gpb-1 cDNA in all neurons rescued both baseline and pathogen PA14-induced ADF tph-1::gfp expression in yz71 mutants. (B) Expressing gpb-1 cDNA specifically in ADF restored baseline tph-1::gfp but not the response to PA14. ADF is the only neuronal type expressed in common by the three transgenes that selectively rescued the baseline ADF tph-1::gfp (the ADF and ADL expression was driven by a lin-11 promoter, and the ADF + others expression was driven by the cat-1 promoter). The transgenes expressed in additional amphid neurons including ADF rescued both the baseline and PA14-induced tph-1::gfp expression, but the transgenes that are not expressed in ADF failed to rescue under either condition. For each assay, the value of ADF GFP fluorescence in WT animals fed PA14 and that of mutants and transgenic animals is normalized to the value of WT animals under optimal conditions. Data represent the average of ≥ 2 trials ± SEM. The differences between yz71 mutants and the transgenic animals under optimal growth conditions are marked on the top of white bars, and the differences between the same strains fed OP50 and PA14 are indicated, ** p < 0.01, *** p < 0.001, ANOVA followed by Tukey tests. (C) Model for GPB-1 regulation of the baseline and pathogen-induced tph-1 expression in ADF. Cell-autonomous GPB-1 is necessary and sufficient for the baseline tph-1 expression. GPB-1 regulates PA14-induced tph-1 upregulation by controlling Gqα EGL-30, which acts in AWB and AWC neurons in the pathogen-induced signaling pathway [25], and other Gα signaling in additional amphid neurons.

Mentions: We first expressed GPB-1 in all neurons, or in hypodermal and glial cells surrounding amphid sensory cilia, or in the gut. Fig 4A shows that expressing GPB-1 in neurons, but not in the other tissues, rescued both the basal and PA14-induced tph-1::gfp expression.


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)

Baseline and pathogen-induced ADF tph-1::gfp expression involve separated GPB-1 functions.(A) Transgenic expressing gpb-1 cDNA in all neurons rescued both baseline and pathogen PA14-induced ADF tph-1::gfp expression in yz71 mutants. (B) Expressing gpb-1 cDNA specifically in ADF restored baseline tph-1::gfp but not the response to PA14. ADF is the only neuronal type expressed in common by the three transgenes that selectively rescued the baseline ADF tph-1::gfp (the ADF and ADL expression was driven by a lin-11 promoter, and the ADF + others expression was driven by the cat-1 promoter). The transgenes expressed in additional amphid neurons including ADF rescued both the baseline and PA14-induced tph-1::gfp expression, but the transgenes that are not expressed in ADF failed to rescue under either condition. For each assay, the value of ADF GFP fluorescence in WT animals fed PA14 and that of mutants and transgenic animals is normalized to the value of WT animals under optimal conditions. Data represent the average of ≥ 2 trials ± SEM. The differences between yz71 mutants and the transgenic animals under optimal growth conditions are marked on the top of white bars, and the differences between the same strains fed OP50 and PA14 are indicated, ** p < 0.01, *** p < 0.001, ANOVA followed by Tukey tests. (C) Model for GPB-1 regulation of the baseline and pathogen-induced tph-1 expression in ADF. Cell-autonomous GPB-1 is necessary and sufficient for the baseline tph-1 expression. GPB-1 regulates PA14-induced tph-1 upregulation by controlling Gqα EGL-30, which acts in AWB and AWC neurons in the pathogen-induced signaling pathway [25], and other Gα signaling in additional amphid neurons.
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getmorefigures.php?uid=PMC4581872&req=5

pgen.1005540.g004: Baseline and pathogen-induced ADF tph-1::gfp expression involve separated GPB-1 functions.(A) Transgenic expressing gpb-1 cDNA in all neurons rescued both baseline and pathogen PA14-induced ADF tph-1::gfp expression in yz71 mutants. (B) Expressing gpb-1 cDNA specifically in ADF restored baseline tph-1::gfp but not the response to PA14. ADF is the only neuronal type expressed in common by the three transgenes that selectively rescued the baseline ADF tph-1::gfp (the ADF and ADL expression was driven by a lin-11 promoter, and the ADF + others expression was driven by the cat-1 promoter). The transgenes expressed in additional amphid neurons including ADF rescued both the baseline and PA14-induced tph-1::gfp expression, but the transgenes that are not expressed in ADF failed to rescue under either condition. For each assay, the value of ADF GFP fluorescence in WT animals fed PA14 and that of mutants and transgenic animals is normalized to the value of WT animals under optimal conditions. Data represent the average of ≥ 2 trials ± SEM. The differences between yz71 mutants and the transgenic animals under optimal growth conditions are marked on the top of white bars, and the differences between the same strains fed OP50 and PA14 are indicated, ** p < 0.01, *** p < 0.001, ANOVA followed by Tukey tests. (C) Model for GPB-1 regulation of the baseline and pathogen-induced tph-1 expression in ADF. Cell-autonomous GPB-1 is necessary and sufficient for the baseline tph-1 expression. GPB-1 regulates PA14-induced tph-1 upregulation by controlling Gqα EGL-30, which acts in AWB and AWC neurons in the pathogen-induced signaling pathway [25], and other Gα signaling in additional amphid neurons.
Mentions: We first expressed GPB-1 in all neurons, or in hypodermal and glial cells surrounding amphid sensory cilia, or in the gut. Fig 4A shows that expressing GPB-1 in neurons, but not in the other tissues, rescued both the basal and PA14-induced tph-1::gfp expression.

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.


Related in: MedlinePlus