%0 Journal Article
%T Cell-Autonomous G¦Â Signaling Defines Neuron-Specific Steady State Serotonin Synthesis in Caenorhabditis elegans
%A Lu Xu&nbsp
%A Sunju Choi&nbsp
%A Yusu Xie&nbsp
%A Ji Ying Sze
%J PLOS Genetics
%D 2015
%I Public Library of Science (PLoS)
%R 10.1371/journal.pgen.1005540
%X Heterotrimeric G proteins regulate a vast array of cellular functions via specific intracellular effectors. Accumulating pharmacological and biochemical studies implicate G¦Â 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¦Á subunit activities. However, the native biological roles of G¦Â-mediated signaling pathways in vivo have been characterized only in a few cases. Here, we identified a G¦Â 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¦Â 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¦Â-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.
%U http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1005540