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Methylation of the sterol nucleus by STRM-1 regulates dauer larva formation in Caenorhabditis elegans

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Entchev,  Eugeni V
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Mende,  Fanny
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Boytchev,  Hristio
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Zagoriy,  Vyacheslav
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Kurzchalia,  Teymuras V
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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引用

Hannich, J. T., Entchev, E. V., Mende, F., Boytchev, H., Martin, R., Zagoriy, V., Theumer, G., Riezman, I., Riezman, H., Knolker, H.-J., & Kurzchalia, T. V. (2009). Methylation of the sterol nucleus by STRM-1 regulates dauer larva formation in Caenorhabditis elegans. Dev Cell, 16(6), 833-843.


引用: https://hdl.handle.net/21.11116/0000-0001-0D49-0
要旨
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.