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
リソース情報
線虫 tm2308