Methylation of the Sterol Nucleus by STRM-1 Regulates Dauer Larva Formation in Caenorhabditis elegans
Methylation of the Sterol Nucleus by STRM-1 Regulates Dauer Larva Formation in Caenorhabditis elegans
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DOI：
10.1016/j.devcel.2009.04.012
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发表时间：
2009-06-16
影响因子：
11.8
通讯作者：
Kurzchalia, Teymuras V.
中科院分区：
文献类型：
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作者：
Hannich, J. Thomas;Entchev, Eugeni V.;Kurzchalia, Teymuras V.
秀丽隐杆线虫对信息素的反应是中断其生殖生活史，进入滞育，成为一种抗应激的幼虫。这个决定是由一个复杂的神经元和激素调节系统控制的。所有的信号都集中在核激素受体12上。一种甾醇衍生的激素，达法膦酸（DA），通过与β-12结合并抑制其促进子代的活性来支持生殖发育。在这里，我们确定了甲基转移酶，STRM-1，调节DA水平，从而dauer形成。通过修饰用于合成DA的底物，STRM-1可以减少产生的激素的量。STRM-1功能的丧失导致DA水平升高和低效的dauer形成。甾醇甲基化以前没有被认为是调节激素活性的机制。此外，由STRM-1催化的C-4固醇核甲基化是线虫所特有的，因此可能是针对寄生线虫感染的治疗策略的靶标。
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.