Methylation of the Sterol Nucleus by STRM-1 Regulates Dauer Larva Formation in Caenorhabditis elegans

作者：Hannich J Thomas; Entchev Eugeni V; Mende Fanny; Boytchev Hristio; Martin Rene; Zagoriy Vyacheslav; Theumer Gabriele; Riezman Isabelle; Riezman Howard; Knoelker Hans Joachim; Kurzchalia Teymuras V^*

来源：Developmental Cell, 2009, 16(6): 833-843.

DOI：10.1016/j.devcel.2009.04.012

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.

• 出版日期2009-6-16