STR-33, a Novel G Protein-coupled Receptor That Regulates Locomotion and Egg Laying in Caenorhabditis elegans

Lee, Jeong Eui; Jeong, Pan Young; Joo, Hyoe Jin; Kim, Heekyeong; Lee, Taehoon; Koo, Hyeon Sook; Paik, Young Ki

doi:10.1074/jbc.m111.241000

Cited by 5 publications

(3 citation statements)

References 37 publications

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“…Since the tph-1 mutant is known to exhibit abnormality in food sensation and ingestion in C. elegans, we sought to confirm that R02D3.7 is not expressed in serotonergic neurons. To this end, we constructed transgenic lines that co-expressed R02D3.7::mCherry and tph-1::GFP from their native promoters and examined overlap [26,27]. Our analysis confirmed that R02D3.7 and tph-1 are expressed in different neuronal cells (Figure 2B).…”

Section: R02d37 Is Expressed In Dopaminergic Neuronsmentioning

confidence: 57%

“…Regarding the dopaminergic neuron-specific expression of rcat-1, previous studies of the effects of serotonin on locomotion during food searching [5,46] and our results from serotonin biosynthesis mutants do not support a serotonergic signaling pattern (Figure 2B). In fact, tph-1(mg280), a TH mutant [27], exhibited no change in food-search behavior (Figure 2C). Taken together, our findings indicate that rcat-1 may be involved in the negative feedback regulation of dopamine metabolism (synthesis and release) in a cell type-specific manner (dopaminergic neurons).…”

Section: Discussionmentioning

confidence: 99%

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

Jeong

Park

Lee

et al. 2022

IJMS

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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.

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Section: R02d37 Is Expressed In Dopaminergic Neuronsmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

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

Jeong

Park

Lee

et al. 2022

IJMS

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“…We find that metformin significantly improves fecundity in worms that express Aβ (Figure 7.3). As ACh and serotonin signaling both modulate egg laying behaviour in C. elegans [579][580][581][582][583][584], it is entirely possible that the improvement in fecundity and egg viability by metformin results from improved function of these signaling systems. The metformin mediated increase in fecundity reflects a decrease in Aβ-mediated toxicity in adults, whereas the improved egg viability probably reflects a decrease in Aβ toxicity at the embryonic stage of development.…”

Section: Discussionmentioning

confidence: 99%

Metabolic study of Alzheimer’s disease using mutant C. elegans

Ahmad¹

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Alzheimer's disease (AD) is associated with chronic neurodegeneration and is the cause of the most common form of dementia. The main hallmarks of AD are aggregates of amyloid beta (Aβ) and formation of hyperphosphorylated tau neurofibrillary tangles (NFTs). Unfortunately, after more than 100 years of research the exact cause(s) and mechanisms involved in AD progression remain unclarified. Evidence indicates that impaired mitochondrial bioenergetics may precede by decades, the neurodegeneration and cognitive decline associated with AD. Moreover, a genetic association of the core metabolic enzyme dihydrolipoamide dehydrogenase (DLD) with late-onset AD and reduced activity of DLD-containing enzymes suggests glucose hypo-metabolism as a possible cause of AD. Contrary to this, improvements of AD symptoms under caloric restriction or other means of reducing-glucose dependent energy metabolism supports an alternative hypothesis that a decrease in glucose metabolism may be protective. In the present study, we used mutant Caenorhabditis elegans (C. elegans) to investigate the effect of glucose metabolism on AD progression. We initially looked at the role of suppressed DLD-1, and then we focused on the effect of high glucose in AD pathogenesis.Transgenic expression of Aβ in C. elegans causes both phenotypic and behavioral defects and results in accumulation of toxic Aβ oligomers, culminating in protein aggregation as is normally associated with AD pathophysiology. Aβ expression in worm muscle causes agedependent progressive paralysis and impaired acetylcholine neurotransmission while neuronal Aβ expression results in defective chemotaxis and impaired serotonin sensitivity as well as reduced fecundity and egg hatching. Suppression of the dld-1 gene alleviated paralysis, improved acetylcholine neurotransmission, enhanced chemotaxis and restored normal sensitivity to serotonin.dld-1 gene suppression also protects vitality as indicated by improved fecundity and egg hatching.Interestingly, protective effects of dld-1 suppression could be reversed using the calcium ionophore (CaI), indicating that the protective mechanism involves calcium signaling. Each of these beneficial effects of dld-1 gene suppression could be mimicked using a specific, small molecule inhibitor of the DLD-1 enzyme, 5-methoxyindole-2-carboxylic acid (MICA).High glucose levels are associated with the metabolic disorder, diabetes, which is a major risk factor for AD. In fact, it has been suggested that AD is a neural form of diabetes, type 3 diabetes. If true, drugs used to treat diabetes could act as possible treatments for AD. In this study, I investigated the effect of elevated glucose, the glucose metabolism inhibitor, 2-deoxy-d-glucose ii (2DOG) as well as the anti-diabetes drugs, metformin and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on AD progression. Elevated glucose in the growth medium induced hyperactivity, which interfered with the paralysis assays, but it was seen to impair cholinergic neurotransmission, egg laying and hatc...

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Metformin Attenuates Aβ Pathology Mediated Through Levamisole Sensitive Nicotinic Acetylcholine Receptors in a C. elegans Model of Alzheimer’s Disease

Ahmad

Ebert

2016

Mol Neurobiol

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The metabolic disease, type 2 diabetes mellitus (T2DM), is a major risk factor for Alzheimer's disease (AD). This suggests that drugs such as metformin that are used to treat T2DM may also be therapeutic toward AD and indicates an interaction between AD and energy metabolism. In this study, we have investigated the effects of metformin and another T2DM drug, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) in C. elegans expressing human Aβ. We found that Aβ expressed in muscle inhibited levamisole sensitive nicotinic acetylcholine receptors and that metformin delayed Aβ-linked paralysis and improved acetylcholine neurotransmission in these animals. Metformin also moderated the effect of neuronal expression of Aβ: decreasing hypersensitivity to serotonin, restoring normal chemotaxis, and improving fecundity. Metformin was unable to overcome the small effect of neuronal Aβ on egg viability. The protective effects of metformin were associated with a decrease in the amount of toxic, oligomeric Aβ. AICAR has a similar protective effect against Aβ toxicity. This work supports the notion that anti-diabetes drugs and metabolic modulators may be effective against AD and that the worm model can be used to identify the specific interactions between Aβ and cellular proteins.

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STR-33, a Novel G Protein-coupled Receptor That Regulates Locomotion and Egg Laying in Caenorhabditis elegans

Cited by 5 publications

References 37 publications

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

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

Metabolic study of Alzheimer’s disease using mutant C. elegans

Metformin Attenuates Aβ Pathology Mediated Through Levamisole Sensitive Nicotinic Acetylcholine Receptors in a C. elegans Model of Alzheimer’s Disease

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