In C. elegans, the tryptophan hydroxylase gene
tph-1 is required for serotonin biosynthesis. Previous studies from our lab and others have identified three layers of regulation for
tph-1 gene expression in the chemosensory neurons ADF. OCR-2/TRPV channel-mediated Ca2+ signaling is required for steady state
tph-1 expression[1]. Pathogen infection and aversive growth conditions that induce dauer formation further increase
tph-1 transcription via UNC-43/TIR-1/MAPK signaling and IFT/Hh-related pathways, respectively[2,3,4]. To further delineate genetic pathways defining steady state 5-HT synthesis, we have carried out a genetic screen for mutants that display reduced
tph-1 expression in ADF neurons under optimal growth conditions. We identified
yz71, a loss-of-function point mutation of the G-protein beta subunit gene
gpb-1. The G162E substitution at the conserved site for Gbeta interacting with the switch II sites of Galpha does not alter ADF cell fates or affects
tph-1 expression in other 5-HT-producing neurons. In addition to setting the steady state
tph-1 expression,
gpb-1 is also required for pathogen-induced
tph-1 upregulation in ADF, although it is dispensable for dauer-induced
tph-1 upregulation. We will present data indicating that steady state and pathogen-induced
tph-1 expression is mediated by distinct
gpb-1 functions. First,
gpb-1 acts in multiple amphid neurons to mediate pathogen-induced
tph-1 upregulation, and in contrast, cell-autonomous
gpb-1 is necessary and sufficient for OCR-2/TRPV channel-regulated steady state
tph-1 expression. Second, while pathogen-induced
tph-1 upregulation requires Gqalpha EGL-30[5], we show that a GPB-1 signaling controls steady state
tph-1 expression. These data revealed a Gbeta signaling in neurons and indicate that steady state serotonin biosynthesis is regulated by neural activities in a cell-specific manner.References1. Zhang S, Sokolchik I, Blanco G, Sze JY. Development 131(7):1629-38, 2004.2. Moussaif M, Sze JY. J Neurosci 29(13):4065-75, 2009.3. Shivers RP, Kooistra T, Chu SW, Pagano DJ, Kim DH. Cell Host Microbe 6(4):321-30, 2009.4. Xie Y, Moussaif M, Choi S, Xu L, Sze JY. PLos Genet 9(3):
e1003324, 2013.5. Qin Y, Zhang X, Zhang Y. J Neurosci 33(3):925-935, 2013.