Forward Genetic Analysis to Identify Determinants of Dopamine Signaling inCaenorhabditis elegansUsing Swimming-Induced Paralysis
| Autor: | J. Andrew Hardaway, Daniel P. Bermingham, Bing Zhang, Ariana J Lichtenstein, Sarah M. Whitaker, Sarah R Baas, Shannon L. Hardie, Randy D. Blakely |
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| Rok vydání: | 2012 |
| Předmět: |
Reserpine
presynaptic Dopamine receptor Mutant Motor Activity Investigations Biology medicine.disease_cause Polymorphism Single Nucleotide Animals Genetically Modified 03 medical and health sciences 0302 clinical medicine Genetics medicine Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Gene Swimming Genetics (clinical) 030304 developmental biology Dopamine Plasma Membrane Transport Proteins 0303 health sciences Mutation Adrenergic Uptake Inhibitors Transporter biology.organism_classification Phenotype Forward genetics forward genetics transporter Signal transduction 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | G3: Genes|Genomes|Genetics |
| ISSN: | 2160-1836 |
| DOI: | 10.1534/g3.112.003533 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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