Regulation of Serotonin Biosynthesis by the G Proteins Gαo and Gαq Controls Serotonin Signaling inCaenorhabditis elegans

Abstract

To analyze mechanisms that modulate serotonin signaling, we investigated how Caenorhabditis elegans regulates the function of serotonergic motor neurons that stimulate egg-laying behavior. Egg laying is inhibited by the G protein Ga o and activated by the G protein Ga q . We found that Ga o and Ga q act directly in the serotonergic HSN motor neurons to control egg laying. There, the G proteins had opposing effects on transcription of the tryptophan hydroxylase gene tph-1, which encodes the rate-limiting enzyme for serotonin biosynthesis. Antiserotonin staining confirmed that Ga o and Ga q antagonistically affect serotonin levels. Altering tph-1 gene dosage showed that small changes in tph-1 expression were sufficient to affect egglaying behavior. Epistasis experiments showed that signaling through the G proteins has additional tph-1-independent effects. Our results indicate that (1) serotonin signaling is regulated by modulating serotonin biosynthesis and (2) Ga o and Ga q act in the same neurons to have opposing effects on behavior, in part, by antagonistically regulating transcription of specific genes. Ga o and Ga q have opposing effects on many behaviors in addition to egg laying and may generally act, as they do in the egg-laying system, to integrate multiple signals and consequently set levels of transcription of genes that affect neurotransmitter release.

STR-33, a Novel G Protein-coupled Receptor That Regulates Locomotion and Egg Laying in Caenorhabditis elegans

“…Consistent with this, we found that tph-1 expression was increased in goa-1(n1134) mutants (data not shown), as previously reported (10). As a first step toward confirming whether the hyperactive egg-laying behavior of str-33(ykp001) mutants was due to changed tph-1 expression in HSNs, we transfected these animals with a tph-1::gfp construct.…”

“…Unexpectedly, str-33 was not expressed in HSNs or VC neurons, which are directly involved in egg-laying behavior (6,10). However, it was detected in ALM and PLM mechanosensory neurons and head neurons (Fig.…”

“…Expression of the tph-1 gene, which encodes tryptophan hydroxylase-1, is strongly suppressed by GOA-1/G␣ o ; conversely, tph-1 expression is activated by EGL-30/G␣ q . Thus, signaling through G o suppresses egg laying by inhibiting 5-HT biosynthesis in HSNs, whereas G q -mediated signaling stimulates 5-HT biosynthesis and egg laying (9,10).…”

“…HSNs make neuromuscular junctions with vulval muscles and VC motor neurons, which are cholinergic neurons that inhibit egg laying by inhibiting HSNs. ACh signaling through a putative GPCR coupled to the G protein GOA-1/G␣ o in HSNs suppresses the egg-laying behavior of C. elegans by inhibiting biosynthesis or release of newly synthesized 5-hydroxytryptamine (5-HT) (6,10). Expression of the tph-1 gene, which encodes tryptophan hydroxylase-1, is strongly suppressed by GOA-1/G␣ o ; conversely, tph-1 expression is activated by EGL-30/G␣ q .…”

Beyond a neurotransmitter: The role of serotonin in plants

“…In vertebrates, serotonin is produced from the essential aromatic amino acid tryptophan via the neuroactive compound 5-hydroxytryptophan (5-HTP) by first a hydroxylation reaction catalyzed by tryptophan hydroxylase (TPH), which is then followed by decarboxylation by aromatic amino acid decarboxylase (AADC) [14] . Similarly, plants first synthesize tryptophan via the chorismate pathway which is then decarboxylated by tryptophan decarboxylase (TDC) to form tryptamine, another bioactive amino acid and common secondary metabolite precursor.…”