論文 - 詳細
| RRC ID | 76221 |
|---|---|
| 著者 | Li N, Hua B, Chen Q, Teng F, Ruan M, Zhu M, Zhang L, Huo Y, Liu H, Zhuang M, Shen H, Zhu H. |
| タイトル | A sphingolipid-mTORC1 nutrient-sensing pathway regulates animal development by an intestinal peroxisome relocation-based gut-brain crosstalk. |
| ジャーナル | Cell Rep |
| Abstract |
The mTOR-dependent nutrient-sensing and response machinery is the central hub for animals to regulate their cellular and developmental programs. However, equivalently pivotal nutrient and metabolite signals upstream of mTOR and developmental-regulatory signals downstream of mTOR are not clear, especially at the organism level. We previously showed glucosylceramide (GlcCer) acts as a critical nutrient and metabolite signal for overall amino acid levels to promote development by activating the intestinal mTORC1 signaling pathway. Here, through a large-scale genetic screen, we find that the intestinal peroxisome is critical for antagonizing the GlcCer-mTORC1-mediated nutrient signal. Mechanistically, GlcCer deficiency, inactive mTORC1, or prolonged starvation relocates intestinal peroxisomes closer to the apical region in a kinesin- and microtubule-dependent manner. Those apical accumulated peroxisomes further release peroxisomal-β-oxidation-derived glycolipid hormones that target chemosensory neurons and downstream nuclear hormone receptor DAF-12 to arrest the animal development. Our data illustrate a sophisticated gut-brain axis that predominantly orchestrates nutrient-sensing-dependent development in animals. |
| 巻・号 | 40(4) |
| ページ | 111140 |
| 公開日 | 2022-7-26 |
| DOI | 10.1016/j.celrep.2022.111140 |
| PII | S2211-1247(22)00949-4 |
| PMID | 35905721 |
| MeSH | Animals Brain / metabolism Mechanistic Target of Rapamycin Complex 1 / metabolism Nutrients Peroxisomes* / metabolism Sphingolipids* / metabolism TOR Serine-Threonine Kinases / metabolism |
| 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 | 14 |
| 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 | tm1027 tm1192 tm504 tm1964 tm6454 tm6502 tm11887 tm4948 |