Deficiency in RCAT-1 Function Causes Dopamine Metabolism Related Behavioral Disorders in Caenorhabditis elegans

Autor: Haelim Jeong, Jun Young Park, Ji-Hyun Lee, Ja-Hyun Baik, Chae-Yeon Kim, Jin-Young Cho, Monica Driscoll, Young-Ki Paik
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 23, Iss 4, p 2393 (2022)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms23042393
Popis: 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.
Databáze: Directory of Open Access Journals
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