G protein-coupled receptor kinase-2 (GRK-2) regulates serotonin metabolism through the monoamine oxidase AMX-2 in Caenorhabditis elegans

@article{Wang2017GPR,
  title={G protein-coupled receptor kinase-2 (GRK-2) regulates serotonin metabolism through the monoamine oxidase AMX-2 in Caenorhabditis elegans},
  author={Jianjun Wang and Jiansong Luo and Dipendra K. Aryal and William C. Wetsel and Richard Nass and Jeffrey L. Benovic},
  journal={The Journal of Biological Chemistry},
  year={2017},
  volume={292},
  pages={5943 - 5956}
}
G protein-coupled receptors (GPCRs) regulate many animal behaviors. GPCR signaling is mediated by agonist-promoted interactions of GPCRs with heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. To further elucidate the role of GRKs in regulating GPCR-mediated behaviors, we utilized the genetic model system Caenorhabditis elegans. Our studies demonstrate that grk-2 loss-of-function strains are egg laying-defective and contain low levels of serotonin (5-HT) and high levels of the 5-HT… 

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References

SHOWING 1-10 OF 55 REFERENCES
The G-Protein-Coupled Serotonin Receptor SER-1 Regulates Egg Laying and Male Mating Behaviors in Caenorhabditis elegans
TLDR
It is shown that SER-1 is the 5- HT GPCR responsible for the stimulatory effects of exogenous 5-HT in two sexually dimorphic behaviors of Caenorhabditis elegans, egg laying and male ventral tail curling.
Structural Domains Required for Caenorhabditis elegans G Protein-coupled Receptor Kinase 2 (GRK-2) Function in Vivo*
TLDR
This is the first study to systematically determine the residues required for GRK function in live animals and demonstrated functional roles for broadly conserved GRK2/3 structural domains in the in vivo regulation of organismal behavior.
Selective Regulation of Gαq/11 by an RGS Domain in the G Protein-coupled Receptor Kinase, GRK2*
TLDR
In vitro analysis revealed that GRK2 possesses weak GAP activity toward Gαq that is dependent on the presence of a G protein-coupled receptor, and data suggest that a subfamily of the GRKs may be bifunctional regulators of G Protein-Coupled receptors signaling operating directly on both receptors and G proteins.
Regulation of Serotonin Biosynthesis by the G Proteins Gαo and Gαq Controls Serotonin Signaling in Caenorhabditis elegans
TLDR
The results indicate that (1) serotonin signaling is regulated by modulating serotonin biosynthesis and (2) Gαo and Gαq act in the same neurons to have opposing effects on behavior, in part, by antagonistically regulating transcription of specific genes.
D1 Dopamine Receptor Signaling Is Modulated by the R7 RGS Protein EAT-16 and the R7 Binding Protein RSBP-1 in Caenoerhabditis elegans Motor Neurons
TLDR
A large-scale dsRNA interference screen in C. elegans found that EAT-16 and RSBP-1 act together to modulate dopamine signaling and that while they are coexpressed with both D1-like and D2-like dopamine receptors, they do not modulate D2 receptor signaling.
Characterization of the Caenorhabditis elegans G protein-coupled serotonin receptors
TLDR
This paper is the first comprehensive study of G protein-coupled serotonin receptors of C. elegans and tests whether the most likely candidate receptors were able to modulate adenylate cyclase activity in transfected cells in a 5-HT-dependent manner.
Caenorhabditis elegans TRPV Channels Function in a Modality-Specific Pathway to Regulate Response to Aberrant Sensory Signaling
TLDR
It is shown here that loss-of-function mutations in the transient receptor potential vanilloid (TRPV) channels OSM-9 and OCR-2 selectively restore grk-2 behavioral avoidance of bitter tastants, revealing modality-specific mechanisms for TRPV channel function in the regulation of C. elegans chemosensation and suggesting a novel mechanism and multiple modalities-specific pathways that sensory cells employ in response to aberrant signal transduction.
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