論文 - 詳細
| RRC ID | 75986 |
|---|---|
| 著者 | Khanna A, Sellegounder D, Kumar J, Chamoli M, Vargas M, Chinta SJ, Rane A, Nelson C, Peiris TH, Brem R, Andersen J, Lithgow G, Kapahi P. |
| タイトル | Trimethylamine modulates dauer formation, neurodegeneration, and lifespan through tyra-3/daf-11 signaling in Caenorhabditis elegans. |
| ジャーナル | Aging Cell |
| Abstract |
In the nematode Caenorhabditis elegans, signals derived from bacteria in the diet, the animal's major nutrient source, can modulate both behavior and healthspan. Here we describe a dual role for trimethylamine (TMA), a human gut flora metabolite, which acts as a nutrient signal and a neurotoxin. TMA and its associated metabolites are produced by the human gut microbiome and have been suggested to serve as risk biomarkers for diabetes and cardiovascular diseases. We demonstrate that the tyramine receptor TYRA-3, a conserved G protein-coupled receptor (GPCR), is required to sense TMA and mediate its responses. TMA activates guanylyl cyclase DAF-11 signaling through TYRA-3 in amphid neurons (ASK) and ciliated neurons (BAG) to mediate food-sensing behavior. Bacterial mutants deficient in TMA production enhance dauer formation, extend lifespan, and are less preferred as a food source. Increased levels of TMA lead to neural damage in models of Parkinson's disease and shorten lifespan. Our results reveal conserved signaling pathways modulated by TMA in C. elegans that are likely to be relevant for its effects in mammalian systems. |
| 巻・号 | 20(5) |
| ページ | e13351 |
| 公開日 | 2021-5-1 |
| DOI | 10.1111/acel.13351 |
| PMID | 33819374 |
| PMC | PMC8135002 |
| MeSH | Animals Bacteria / enzymology Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Dopaminergic Neurons / pathology Guanylate Cyclase / metabolism* Iron-Sulfur Proteins / genetics Longevity* Methylamines / metabolism* Mutation Oxidoreductases / genetics Receptors, Catecholamine / metabolism* Signal Transduction |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 15 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1325 |