RRC ID 6372
著者 Hannich JT, Entchev EV, Mende F, Boytchev H, Martin R, Zagoriy V, Theumer G, Riezman I, Riezman H, Knölker HJ, Kurzchalia TV.
タイトル Methylation of the sterol nucleus by STRM-1 regulates dauer larva formation in Caenorhabditis elegans.
ジャーナル Dev Cell
Abstract In response to pheromone(s), Caenorhabditis elegans interrupts its reproductive life cycle and enters diapause as a stress-resistant dauer larva. This decision is governed by a complex system of neuronal and hormonal regulation. All the signals converge onto the nuclear hormone receptor DAF-12. A sterol-derived hormone, dafachronic acid (DA), supports reproductive development by binding to DAF-12 and inhibiting its dauer-promoting activity. Here, we identify a methyltransferase, STRM-1, that modulates DA levels and thus dauer formation. By modifying the substrates that are used for the synthesis of DA, STRM-1 can reduce the amount of hormone produced. Loss of STRM-1 function leads to elevated levels of DA and inefficient dauer formation. Sterol methylation was not previously recognized as a mechanism for regulating hormone activity. Moreover, the C-4 sterol nucleus methylation catalyzed by STRM-1 is unique to nematodes and thus could be a target for therapeutic strategies against parasitic nematode infections.
巻・号 16(6)
ページ 833-43
公開日 2009-6-1
DOI 10.1016/j.devcel.2009.04.012
PII S1534-5807(09)00174-9
PMID 19531354
MeSH Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / enzymology Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cholestenes / metabolism Cholesterol / metabolism Cytochrome P-450 Enzyme System / metabolism Gene Deletion Gene Expression Regulation, Developmental / drug effects Larva / cytology Larva / drug effects Larva / growth & development Larva / metabolism Methylation / drug effects Methyltransferases / genetics Methyltransferases / metabolism* Models, Biological Pheromones / pharmacology Protein Methyltransferases / metabolism Receptors, Cytoplasmic and Nuclear / metabolism Sterols / chemistry Sterols / metabolism* Substrate Specificity / drug effects
IF 10.092
引用数 33
WOS 分野 DEVELOPMENTAL BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm1781