論文 - 詳細
| RRC ID | 4277 |
|---|---|
| 著者 | Patel DS, Fang LL, Svy DK, Ruvkun G, Li W. |
| タイトル | Genetic identification of HSD-1, a conserved steroidogenic enzyme that directs larval development in Caenorhabditis elegans. |
| ジャーナル | Development |
| Abstract |
In C. elegans, steroid hormones function in conjunction with insulin/IGF-1-like signaling in promoting reproductive development over entry into the diapausal dauer stage. The NCR-1 and -2 (NPC1-related) intracellular cholesterol transporters function redundantly in preventing dauer arrest, presumably by regulating the availability of substrates for steroid hormone synthesis. We have identified hsd-1 as a new component of this cholesterol trafficking/processing pathway, using an ncr-1 enhancer screen. HSD-1 is orthologous to 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerases (3beta-HSDs), which are key steroidogenic enzymes in vertebrates, and is exclusively expressed in two neuron-like XXX cells that are crucial in preventing dauer arrest, suggesting that it is involved in biosynthesis of dauer-preventing steroid hormones. The hsd-1 null mutant displays defects in inhibiting dauer arrest: it forms dauers in the deletion mutant backgrounds of ncr-1 or daf-28/insulin; as a single mutant, it is hypersensitive to dauer pheromone. We found that hsd-1 defects can be rescued by feeding mutant animals with several steroid intermediates that are either downstream of or in parallel to the 3beta-HSD function in the dafachronic acid biosynthetic pathway, suggesting that HSD-1 functions as a 3beta-HSD. Interestingly, sterols that rescued hsd-1 defects also bypassed the need for the NCR-1 and/or -2 functions, suggesting that HSD-1-mediated steroid hormone production is an important functional output of the NCR transporters. Finally, we found that the HSD-1-mediated signal activates insulin/IGF-I signaling in a cell non-autonomous fashion, suggesting a novel mechanism for how these two endocrine pathways intersect in directing development. |
| 巻・号 | 135(13) |
| ページ | 2239-49 |
| 公開日 | 2008-7-1 |
| DOI | 10.1242/dev.016972 |
| PII | dev.016972 |
| PMID | 18495818 |
| MeSH | 3-Hydroxysteroid Dehydrogenases / genetics 3-Hydroxysteroid Dehydrogenases / metabolism* Animals Biological Transport Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Endocrine System / metabolism Gene Expression Regulation, Developmental* Isoenzymes / genetics Isoenzymes / metabolism Larva / enzymology Larva / genetics Larva / growth & development Membrane Proteins / genetics Membrane Proteins / metabolism* Membrane Transport Proteins / metabolism Molecular Structure Phenotype Reproduction Signal Transduction Steroids / biosynthesis* Steroids / chemistry |
| IF | 5.611 |
| 引用数 | 36 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 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 | tm2308 |