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

Lu Xu, Sunju Choi, Yusu Xie, Ji Ying Sze

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1005540
JournalPLoS Genetics
Volume11
Issue number9
DOIs
StatePublished - 2015

Fingerprint

Gastrin-Secreting Cells
Caenorhabditis elegans
serotonin
Serotonin
neurons
Neurons
synthesis
innate behavior
Instinct
cells
Tryptophan Hydroxylase
Serotonergic Neurons
Heterotrimeric GTP-Binding Proteins
nervous system
G-proteins
tryptophan
Nervous System
functional properties
Up-Regulation
Pharmacology

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Cell-Autonomous Gβ Signaling Defines Neuron-Specific Steady State Serotonin Synthesis in Caenorhabditis elegans. / Xu, Lu; Choi, Sunju; Xie, Yusu; Sze, Ji Ying.

In: PLoS Genetics, Vol. 11, No. 9, e1005540, 2015.

Research output: Contribution to journalArticle

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