Title: | Deficiency in RCAT-1 Function Causes Dopamine Metabolism Related Behavioral Disorders in Caenorhabditis elegans |
Author(s): | Jeong H; Park JY; Lee JH; Baik JH; Kim CY; Cho JY; Driscoll M; Paik YK; |
Address: | "Department of Biochemistry, College of Life Sciences and Biotechnology, Yonsei University, Seoul 03722, Korea. Yonsei Proteome Research Center, Yonsei University, Seoul 03722, Korea. Department of Life Sciences, Korea University, Seoul 02841, Korea. Interdisciplinary Program in Integrative Omics for Biomedical Science, Yonsei University, Seoul 03722, Korea. Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08855, USA" |
ISSN/ISBN: | 1422-0067 (Electronic) 1422-0067 (Linking) |
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" |
Keywords: | "Animals Animals, Genetically Modified/metabolism Behavior, Animal/*physiology Caenorhabditis elegans/*metabolism/*physiology Caenorhabditis elegans Proteins/*metabolism Dopamine/*metabolism Dopaminergic Neurons/metabolism Gene Expression Regulation/physio;" |
Notes: | "MedlineJeong, Haelim Park, Jun Young Lee, Ji-Hyun Baik, Ja-Hyun Kim, Chae-Yeon Cho, Jin-Young Driscoll, Monica Paik, Young-Ki eng P40 OD010440/OD/NIH HHS/ 2017R1A2B3003200/National Research Foundation of Korea/ Switzerland 2022/02/27 Int J Mol Sci. 2022 Feb 21; 23(4):2393. doi: 10.3390/ijms23042393" |