Dopamine signaling in C. elegans is mediated in part by HLH-17-dependent regulation of extracellular dopamine levels.
In Caenorhabditis elegans, the dopamine transporter DAT-1 regulates synaptic dopamine (DA) signaling by controlling extracellular DA levels. In dat-1(ok157) animals, DA is not taken back up presynaptically but instead reaches extrasynpatic sites, where it activates the dopamine receptor DOP-3 on choligeneric motor neurons and causes animals to become paralyzed in water. This phenotype is called swimming-induced paralysis (SWIP) and is dependent on dat-1 and dop-3. Upstream regulators of dat-1 and dop-3 have yet to be described in C. elegans. In our previous studies, we defined a role for HLH-17 during dopamine response through its regulation of the dopamine receptors. Here we continue our characterization of the effects of HLH-17 on dopamine signaling. Our results suggest that HLH-17 acts downstream of dopamine synthesis to regulate the expression of dop-3 and dat-1. First, we show that hlh-17 animals display a SWIP phenotype that is consistent with its regulation of dop-3 and dat-1. Second, we show that this behavior is enhanced by treatment with the dopamine reuptake inhibitor, bupropion, in both hlh-17 and dat-1 animals, a result suggesting that SWIP behavior is regulated via a mechanism that is both dependent on and independent of DAT-1. Third, and finally, we show that although the SWIP phenotype of hlh-17 animals is unresponsive to the dopamine agonist, reserpine, and to the antidepressant, fluoxetine, hlh-17 animals are not defective in acetylcholine signaling. Taken together, our work suggests that HLH-17 is required to maintain normal levels of dopamine in the synaptic cleft through its regulation of dop-3 and dat-1.
Department of Biology, School of Arts and Sciences, Georgia State University, Atlanta, Georgia 30303.
Chaquettea M
CM
Felton
Department of Biology, School of Arts and Sciences, Georgia State University, Atlanta, Georgia 30303 cjohnson113@gsu.edu.
Casonya M
CM
Johnson
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D055786:Gene Knockout Techniques; D008297:Male; D009154:Mutation; D010641:Phenotype; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C494134:DOP-3 protein, C elegans; C504333:HLH-17 protein, C elegans; D017448:Receptors, Dopamine D2; D014157:Transcription Factors; D012701:Serotonin; D000109:Acetylcholine; D004298:Dopamine
acetylcholine signaling; bupropion; dopamine receptor; fluoxetine; reserpine