Deficiency in RCAT-1 Function Causes Dopamine Metabolism Related Behavioral Disorders in Caenorhabditis elegans
- Authors
- Jeong, H.; Park, J.Y.; Lee, J.-H.; Baik, J.-H.; Kim, C.-Y.; Cho, J.-Y.; Driscoll, M.; Paik, Y.-K.
- Issue Date
- 2월-2022
- Publisher
- MDPI
- Keywords
- C. elegans; Dopamine; Dopamine dysregulation syndrome; Parkinson’s disease; Tyrosine hydroxylase; Vesicular monoamine transporter
- Citation
- International Journal of Molecular Sciences, v.23, no.4
- Indexed
- SCIE
SCOPUS
- Journal Title
- International Journal of Molecular Sciences
- Volume
- 23
- Number
- 4
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/140322
- DOI
- 10.3390/ijms23042393
- ISSN
- 1661-6596
- Abstract
- When animals are faced with food depletion, food search-associated locomotion is crucial for their survival. Although food search-associated locomotion is known to be regulated by dopamine, it has yet to investigate the potential molecular mechanisms governing the regulation of genes involved in dopamine metabolism (e.g., cat-1, cat-2) and related behavioral disorders. During the studies of the pheromone ascaroside, a signal of starvation stress in C. elegans, we identified R02D3.7, renamed rcat-1 (regulator of cat genes-1), which had previously been shown to bind to regulatory sequences of both cat-1 and cat-2 genes. It was found that RCAT-1 (R02D3.7) is expressed in dopaminergic neurons and functions as a novel negative transcriptional regulator for cat-1 and cat-2 genes. When a food source becomes depleted, the null mutant, rcat-1(ok1745), exhibited an increased frequency of high-angled turns and intensified area restricted search behavior compared to the wild-type animals. Moreover, rcat-1(ok1745) also showed defects in state-dependent olfactory adaptation and basal slowing response, suggesting that the mutants are deficient in either sensing food or locomotion toward food. However, rcat-1(ok1745) has normal cuticular structures and locomotion genes. The discovery of rcat-1 not only identifies a new subtype of dopamine-related behaviors but also provides a potential therapeutic target in Parkinson’s disease. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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