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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.


gpb-1(yz71) does not abrogate ADF cell fates.(A) Visualizing amphid neuronal architecture in living animals using DiI filling. In yz71 mutants, DiI filled into the typical 6 pairs of amphid neurons, although the dye could sometimes be detected in several additional neurons (arrowheads). (B) ADF-specific marker Psrh-142::mCherry was expressed and showed characteristic ADF cilia structure (insets) in yz71 mutants. (C) GFP-tagged VMAT CAT-1 protein was expressed in ADF of yz71 mutants. Animals at all developmental stages were examined, and images of L4 animals are shown.
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pgen.1005540.g002: gpb-1(yz71) does not abrogate ADF cell fates.(A) Visualizing amphid neuronal architecture in living animals using DiI filling. In yz71 mutants, DiI filled into the typical 6 pairs of amphid neurons, although the dye could sometimes be detected in several additional neurons (arrowheads). (B) ADF-specific marker Psrh-142::mCherry was expressed and showed characteristic ADF cilia structure (insets) in yz71 mutants. (C) GFP-tagged VMAT CAT-1 protein was expressed in ADF of yz71 mutants. Animals at all developmental stages were examined, and images of L4 animals are shown.

Mentions: We first determined whether amphid sensory neurons were generated in gpb-1(yz71) mutants, using dye DiI filling. The pair of amphids in the head is the major C. elegans sensory organ, each comprising one ADF and eleven other classes of non-serotonergic sensory neurons with characteristic ciliated sensory endings sensing particular environmental cues [22]. We observed DiI filled into the typical six pairs of the amphid neurons in yz71 mutants as in WT animals (Fig 2A). Judged by DiI fluorescence, the overall neuronal organization and their axonal and dendritic morphology were preserved in yz71 mutants (Fig 2A). However, while DiI rarely filled into ADF neurons in WT animals (8%, N = 26), 31% of ADF were filled with DiI in yz71 mutants (N = 65). DiI also filled into a few non-amphid neurons in some yz71 mutants (Fig 2A).


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)

gpb-1(yz71) does not abrogate ADF cell fates.(A) Visualizing amphid neuronal architecture in living animals using DiI filling. In yz71 mutants, DiI filled into the typical 6 pairs of amphid neurons, although the dye could sometimes be detected in several additional neurons (arrowheads). (B) ADF-specific marker Psrh-142::mCherry was expressed and showed characteristic ADF cilia structure (insets) in yz71 mutants. (C) GFP-tagged VMAT CAT-1 protein was expressed in ADF of yz71 mutants. Animals at all developmental stages were examined, and images of L4 animals are shown.
© Copyright Policy
Related In: Results  -  Collection

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

pgen.1005540.g002: gpb-1(yz71) does not abrogate ADF cell fates.(A) Visualizing amphid neuronal architecture in living animals using DiI filling. In yz71 mutants, DiI filled into the typical 6 pairs of amphid neurons, although the dye could sometimes be detected in several additional neurons (arrowheads). (B) ADF-specific marker Psrh-142::mCherry was expressed and showed characteristic ADF cilia structure (insets) in yz71 mutants. (C) GFP-tagged VMAT CAT-1 protein was expressed in ADF of yz71 mutants. Animals at all developmental stages were examined, and images of L4 animals are shown.
Mentions: We first determined whether amphid sensory neurons were generated in gpb-1(yz71) mutants, using dye DiI filling. The pair of amphids in the head is the major C. elegans sensory organ, each comprising one ADF and eleven other classes of non-serotonergic sensory neurons with characteristic ciliated sensory endings sensing particular environmental cues [22]. We observed DiI filled into the typical six pairs of the amphid neurons in yz71 mutants as in WT animals (Fig 2A). Judged by DiI fluorescence, the overall neuronal organization and their axonal and dendritic morphology were preserved in yz71 mutants (Fig 2A). However, while DiI rarely filled into ADF neurons in WT animals (8%, N = 26), 31% of ADF were filled with DiI in yz71 mutants (N = 65). DiI also filled into a few non-amphid neurons in some yz71 mutants (Fig 2A).

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.