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

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.

An Intricate Network Involving the Argonaute ALG-1 Modulates Organismal Resistance to Oxidative Stress

“…R02D3.7 is a transcription factor carrying the well-conserved C2H2-type zinc finger motif. A study has recently described R02D3.7 as a negative regulator of cat-1 and cat-2 – genes involved in dopamine metabolism in C. elegans - rendering it the name RCAT-1 (regulator of cat genes) 57 . Interestingly, R02D3.7 was identified as responsive to the pheromone ascaroside, which normally serves as a signal of starvation or overcrowding in C. elegans 57 .…”

“…A study has recently described R02D3.7 as a negative regulator of cat-1 and cat-2 – genes involved in dopamine metabolism in C. elegans - rendering it the name RCAT-1 (regulator of cat genes) 57 . Interestingly, R02D3.7 was identified as responsive to the pheromone ascaroside, which normally serves as a signal of starvation or overcrowding in C. elegans 57 . Altogether, these results point to R02D3.7/RCAT-1 as a stress sensor controlling alg-1 transcription and stress response in C. elegans .…”

Sink or swim: Does a worm paralysis phenotype hold clues to neurodegenerative disease?

“…Using the FIF, initial mutagenesis studies led to the identification of lines whose DA FIF was diminished or abolished, leading to the discovery of cat‐1 and cat‐2 genes, now understood to support vesicular transport of DA and DA synthesis, respectively. Over the years, these mutants have been used to identify multiple behaviors that involve DA signaling including movement, basal slowing (Sawin et al, 2000), a motor response of animals when encountering bacteria, area restricted search behavior (Jeong et al, 2022), and tap habituation (Giles & Rankin, 2009). Importantly, as de novo synthesis of DA and DA vesicular storage are not lost with mutations in DAT‐1, screening studies utilizing the FIF phenotype failed to identify dat‐1 mutant animals.…”