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

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Levels of neurotransmitter serotonin synthesis shape disparate behaviors in evolutionary diverse organisms, but the mechanisms defining steady state serotonin synthesis in functionally distinct neuronal types remain unknown. A genetic screen for neuron-specific serotonin synthesis mutants in Caenorhabditis elegans revealed a unique Gβ GPB-1 signaling pathway operating in specific serotonergic neurons to define the baseline expression of serotonin synthesis rate-limiting enzyme tryptophan hydroxylase tph-1. Unlike in canonical heterotrimeric G protein signaling pathways where Gα subunits drive downstream effectors, we found that signaling through Gβ GPB-1 to the OCR-2 TRPV channel defines the baseline tph-1 expression. This Gβ signaling is not required for the establishment or maintenance of the serotonergic cell fates, but dedicated to set steady state 5-HT synthesis in mature neurons. Behavioral analyses showed that 5-HT synthesized in different neurons modulates distinct innate rhythmic behaviors. Our work identified a Gβ-mediated signaling pathway operating in differentiated neuronal cells to specify intrinsic functional diversities, and illuminate a mechanistic principle for genetic programming of neuron-specific steady state 5-HT synthesis in dedicated behavioral circuits.

Vyšlo v časopise: Cell-Autonomous Gβ Signaling Defines Neuron-Specific Steady State Serotonin Synthesis in. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005540
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005540

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