論文 - 詳細
RRC ID | 6372 |
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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 |