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Comments on Xu L et al. (2015) PLoS Genet "Cell-Autonomous G Signaling Defines Neuron-Specific Steady State Serotonin Synthesis in Caenorhabditis elegans." (0)
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Xu L, Choi S, Xie Y, & Sze JY (2015). Cell-Autonomous G Signaling Defines Neuron-Specific Steady State Serotonin Synthesis in Caenorhabditis elegans. PLoS Genet, 11, e1005540. doi:10.1371/journal.pgen.1005540
Heterotrimeric G proteins regulate a vast array of cellular functions via specific intracellular effectors. Accumulating pharmacological and biochemical studies implicate G subunits as signaling molecules interacting directly with a wide range of effectors to modulate downstream cellular responses, in addition to their role in regulating G subunit activities. However, the native biological roles of G-mediated signaling pathways in vivo have been characterized only in a few cases. Here, we identified a G 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 G 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 G-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.