論文 - 詳細
| RRC ID | 45966 |
|---|---|
| 著者 | Ferguson AA, Roy S, Kormanik KN, Kim Y, Dumas KJ, Ritov VB, Matern D, Hu PJ, Fisher AL. |
| タイトル | TATN-1 mutations reveal a novel role for tyrosine as a metabolic signal that influences developmental decisions and longevity in Caenorhabditis elegans. |
| ジャーナル | PLoS Genet |
| Abstract |
Recent work has identified changes in the metabolism of the aromatic amino acid tyrosine as a risk factor for diabetes and a contributor to the development of liver cancer. While these findings could suggest a role for tyrosine as a direct regulator of the behavior of cells and tissues, evidence for this model is currently lacking. Through the use of RNAi and genetic mutants, we identify tatn-1, which is the worm ortholog of tyrosine aminotransferase and catalyzes the first step of the conserved tyrosine degradation pathway, as a novel regulator of the dauer decision and modulator of the daf-2 insulin/IGF-1-like (IGFR) signaling pathway in Caenorhabditis elegans. Mutations affecting tatn-1 elevate tyrosine levels in the animal, and enhance the effects of mutations in genes that lie within the daf-2/insulin signaling pathway or are otherwise upstream of daf-16/FOXO on both dauer formation and worm longevity. These effects are mediated by elevated tyrosine levels as supplemental dietary tyrosine mimics the phenotypes produced by a tatn-1 mutation, and the effects still occur when the enzymes needed to convert tyrosine into catecholamine neurotransmitters are missing. The effects on dauer formation and lifespan require the aak-2/AMPK gene, and tatn-1 mutations increase phospho-AAK-2 levels. In contrast, the daf-16/FOXO transcription factor is only partially required for the effects on dauer formation and not required for increased longevity. We also find that the controlled metabolism of tyrosine by tatn-1 may function normally in dauer formation because the expression of the TATN-1 protein is regulated both by daf-2/IGFR signaling and also by the same dietary and environmental cues which influence dauer formation. Our findings point to a novel role for tyrosine as a developmental regulator and modulator of longevity, and support a model where elevated tyrosine levels play a causal role in the development of diabetes and cancer in people. |
| 巻・号 | 9(12) |
| ページ | e1004020 |
| 公開日 | 2013-1-1 |
| DOI | 10.1371/journal.pgen.1004020 |
| PII | PGENETICS-D-13-00168 |
| PMID | 24385923 |
| PMC | PMC3868569 |
| MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans Proteins / genetics* Forkhead Transcription Factors Gene Expression Regulation, Developmental Green Fluorescent Proteins Humans Insulin / metabolism Insulin-Like Growth Factor I / metabolism Larva / genetics Larva / growth & development Larva / metabolism Longevity / genetics* Metabolic Networks and Pathways / genetics* Mutation RNA Interference Receptor, Insulin / metabolism Transcription Factors / genetics Tyrosine / genetics* Tyrosine / metabolism Tyrosine Transaminase / genetics* |
| IF | 5.175 |
| 引用数 | 28 |
| WOS 分野 | GENETICS & HEREDITY |
| 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 | |
| 各媒体での言及数の合計 | 9 |
| 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 | tm3188 |