Department of Biochemistry, College of Life Sciences and Biotechnology, Yonsei University, Seoul 03722, Korea.
Yonsei Proteome Research Center, Yonsei University, Seoul 03722, Korea.
Int J Mol Sci. 2022 Feb 21;23(4):2393. doi: 10.3390/ijms23042393.
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., ) and related behavioral disorders. During the studies of the pheromone ascaroside, a signal of starvation stress in we identified R02D3.7, renamed (regulator of genes-), which had previously been shown to bind to regulatory sequences of both and genes. It was found that RCAT-1 (R02D3.7) is expressed in dopaminergic neurons and functions as a novel negative transcriptional regulator for and genes. When a food source becomes depleted, the null mutant, , exhibited an increased frequency of high-angled turns and intensified area restricted search behavior compared to the wild-type animals. Moreover, 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, has normal cuticular structures and locomotion genes. The discovery of not only identifies a new subtype of dopamine-related behaviors but also provides a potential therapeutic target in Parkinson's disease.
当动物面临食物匮乏时，与寻找食物相关的运动对于它们的生存至关重要。尽管已知多巴胺调节与寻找食物相关的运动，但尚未研究调节多巴胺代谢相关基因（例如）和相关行为障碍的潜在分子机制。在研究信息素 ascaroside 作为饥饿应激信号时，我们在秀丽隐杆线虫中鉴定出 R02D3.7，将其重新命名为（基因调节因子），先前的研究表明它可以结合到和基因的调节序列上。研究发现 RCAT-1（R02D3.7）在多巴胺能神经元中表达，并作为和基因的新型负转录调节因子发挥作用。当食物源枯竭时，与野生型动物相比，缺失突变体（）表现出高频的大角度转弯和强化的区域限制搜索行为。此外，（）还表现出状态依赖的嗅觉适应和基础减速反应缺陷，表明突变体在感知食物或向食物移动方面存在缺陷。然而，（）的表皮结构和运动基因正常。的发现不仅确定了一种新的与多巴胺相关的行为亚型，而且为帕金森病提供了一个潜在的治疗靶点。
