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

Young-Ki Paik,Heekyeong Kim,Hyoe-Jin Joo,Taehoon Lee,Jeong-Eui Lee,Pan-Young Jeong,Hyeon-Sook Koo

doi:10.1074/jbc.m111.241000

Young-Ki Paik, Heekyeong Kim + Show 5 more

Open Access

https://doi.org/10.1074/jbc.m111.241000

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Abstract

Despite their predicted functional importance, most G protein-coupled receptors (GPCRs) in Caenorhabditis elegans have remained largely uncharacterized. Here, we focused on one GPCR, STR-33, encoded by the str-33 gene, which was discovered through a ligand-based screening procedure. To characterize STR-33 function, we performed UV-trimethylpsolaren mutagenesis and isolated an str-33-null mutant. The resulting mutant showed hypersinusoidal movement and a hyperactive egg-laying phenotype. Two types of egg laying-related mutations have been characterized: egg laying-deficient (Egl-d) and hyperactive egg laying (Egl-c). The defect responsible for the egg laying-deficient Egl-d phenotype is related to Gα(q) signaling, whereas that responsible for the opposite, hyperactive egg-laying Egl-c phenotype is related to Gα(o) signaling. We found that the hyperactive egg-laying defect of the str-33(ykp001) mutant is dependent on the G protein GOA-1/Gα(o). Endogenous acetylcholine suppressed egg laying in C. elegans via a Gα(o)-signaling pathway by inhibiting serotonin biosynthesis or release from the hermaphrodite-specific neuron. Consistent with this, in vivo expression of the serotonin biosynthetic enzyme, TPH-1, was up-regulated in the str-33(ykp001) mutant. Taken together, these results suggest that the GPCR, STR-33, may be one of the neurotransmitter receptors that regulates locomotion and egg laying in C. elegans.

Highlights

Signal transduction through G protein-coupled receptors (GPCRs)4 is conserved from yeast to mammals and mediates cellular processes as diverse as odorant detection, hormonal signaling, vision, and drug responses [1]
Consistent with this, in vivo expression of the serotonin biosynthetic enzyme, TPH-1, was up-regulated in the str-33(ykp001) mutant. These results suggest that the GPCR, STR-33, may be one of the neurotransmitter receptors that regulates locomotion and egg laying in C. elegans
Isolation and Basic Characterization of the str-33 Single Deletion Mutant—During the course of studying daumone signaling-associated proteins, we discovered STR-33, a novel GPCRlike protein that lacks homology to known mammalian proteins 5

Summary

Introduction

Signal transduction through G protein-coupled receptors (GPCRs)4 is conserved from yeast to mammals and mediates cellular processes as diverse as odorant detection, hormonal signaling, vision, and drug responses [1]. The hyperactive egg-laying (11.6 Ϯ 1.4) (Fig. 3D) and the locomotion defect phenotype of str33(ykp001) mutant (supplemental Fig. S3) were suppressed by the mec-4(d) mutation, suggesting that STR-33 GPCR acts in mechanosensory neurons to regulate both egg-laying and locomotion behavior of C. elegans.

Results

Conclusion