RRC ID 46352
著者 Hardaway JA, Hardie SL, Whitaker SM, Baas SR, Zhang B, Bermingham DP, Lichtenstein AJ, Blakely RD.
タイトル Forward genetic analysis to identify determinants of dopamine signaling in Caenorhabditis elegans using swimming-induced paralysis.
ジャーナル G3 (Bethesda)
Abstract Disrupted dopamine (DA) signaling is believed to contribute to the core features of multiple neuropsychiatric and neurodegenerative disorders. Essential features of DA neurotransmission are conserved in the nematode Caenorhabditis elegans, providing us with an opportunity to implement forward genetic approaches that may reveal novel, in vivo regulators of DA signaling. Previously, we identified a robust phenotype, termed Swimming-induced paralysis (Swip), that emerges in animals deficient in the plasma membrane DA transporter. Here, we report the use and quantitative analysis of Swip in the identification of mutant genes that control DA signaling. Two lines captured in our screen (vt21 and vt22) bear novel dat-1 alleles that disrupt expression and surface trafficking of transporter proteins in vitro and in vivo. Two additional lines, vt25 and vt29, lack transporter mutations but exhibit genetic, biochemical, and behavioral phenotypes consistent with distinct perturbations of DA signaling. Our studies validate the utility of the Swip screen, demonstrate the functional relevance of DA transporter structural elements, and reveal novel genomic loci that encode regulators of DA signaling.
巻・号 2(8)
ページ 961-75
公開日 2012-8-1
DOI 10.1534/g3.112.003533
PII GGG_003533
PMID 22908044
PMC PMC3411251
MeSH Adrenergic Uptake Inhibitors / pharmacology Animals Animals, Genetically Modified Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Dopamine / metabolism* Dopamine Plasma Membrane Transport Proteins / genetics Dopamine Plasma Membrane Transport Proteins / metabolism Motor Activity / drug effects Mutation Phenotype Polymorphism, Single Nucleotide Reserpine / pharmacology Signal Transduction / genetics* Swimming
IF 2.781
引用数 17
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm2261