Mechanism of extrasynaptic dopamine signaling in Caenorhabditis elegans

被引:214
作者
Chase, DL [1 ]
Pepper, JS [1 ]
Koelle, MR [1 ]
机构
[1] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nn1316
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:1096 / 1103
页数:8
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