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Mechanism of extrasynaptic dopamine signaling in Caenorhabditis elegans

Nature Neuroscience volume 7, pages 10961103 (2004) | Download Citation

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Abstract

D1-like and D2-like dopamine receptors have synergistic and antagonistic effects on behavior. To understand the mechanisms underlying these effects, we studied dopamine signaling genetically in Caenorhabditis elegans. Knocking out a D2-like receptor, DOP-3, caused locomotion defects similar to those observed in animals lacking dopamine. Knocking out a D1-like receptor, DOP-1, reversed the defects of the DOP-3 knockout. DOP-3 and DOP-1 have their antagonistic effects on locomotion by acting in the same motor neurons, which coexpress the receptors and which are not postsynaptic to dopaminergic neurons. In a screen for mutants unable to respond to dopamine, we identified four genes that encode components of the antagonistic Gαo and Gαq signaling pathways, including Gαo itself and two subunits of the regulator of G protein signaling (RGS) complex that inhibits Gαq. Our results indicate that extrasynaptic dopamine regulates C. elegans locomotion through D1- and D2-like receptors that activate the antagonistic Gαq and Gαo signaling pathways, respectively.

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Acknowledgements

This work was supported by grants from the Michael J. Fox Foundation for Parkinson's Research, the Robert Leet and Clara Guthrie Patterson Trust, the NIH and the Leukemia and Lymphoma Society. Some strains were obtained from the Caenorhabditis Genetics Center, which is supported by the NIH National Center for Research Resources. We thank A. Nairn for helpful discussions and A. Jose for sequencing dgk-1 alleles.

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  1. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.

    • Daniel L Chase
    • , Judy S Pepper
    •  & Michael R Koelle

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Daniel L Chase.

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  1. 1.

    Supplementary Fig. 1

    Schematic representation of the opposing G protein signaling pathways that control locomotion behavior in C. elegans. See text for a description of the Gαo and Gαq pathways. Our results suggest that dopamine decreases locomotion by binding to DOP-3 and activating GOA-1 Gαo signaling, while dopamine also increases locomotion by binding DOP-1 and activating EGL-30 Gαq signaling, and that these events occur within the same cells.

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DOI

https://doi.org/10.1038/nn1316

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