Mechanism of extrasynaptic dopamine signaling in Caenorhabditis elegans.
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 Galpha(o) and Galpha(q) signaling pathways, including Galpha(o) itself and two subunits of the regulator of G protein signaling (RGS) complex that inhibits Galpha(q). Our results indicate that extrasynaptic dopamine regulates C. elegans locomotion through D1- and D2-like receptors that activate the antagonistic Galpha(q) and Galpha(o) signaling pathways, respectively.
Chase
Daniel L
DL
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA. daniel.chase@yale.edu <daniel.chase@yale.edu>
Pepper
Judy S
JS
Koelle
Michael R
MR
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004298:Dopamine / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D018390:Gene Targeting; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000235:genetics; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009420:Nervous System / Q000378:metabolism*; D010802:Phylogeny; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism; D011954:Receptors, Dopamine / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; C494134:DOP-3 protein, C elegans; C488450:Dop-1 protein, C elegans; D020710:RGS Proteins; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C477462:dop-2 protein, C elegans; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D000109:Acetylcholine; D004298:Dopamine