PMID- 19531354 OWN - NLM STAT- MEDLINE DCOM- 20090714 LR - 20131121 IS - 1878-1551 (Electronic) IS - 1534-5807 (Linking) VI - 16 IP - 6 DP - 2009 Jun TI - Methylation of the sterol nucleus by STRM-1 regulates dauer larva formation in Caenorhabditis elegans. PG - 833-43 LID - 10.1016/j.devcel.2009.04.012 [doi] AB - 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. FAU - Hannich, J Thomas AU - Hannich JT AD - Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany. FAU - Entchev, Eugeni V AU - Entchev EV FAU - Mende, Fanny AU - Mende F FAU - Boytchev, Hristio AU - Boytchev H FAU - Martin, Rene AU - Martin R FAU - Zagoriy, Vyacheslav AU - Zagoriy V FAU - Theumer, Gabriele AU - Theumer G FAU - Riezman, Isabelle AU - Riezman I FAU - Riezman, Howard AU - Riezman H FAU - Knolker, Hans-Joachim AU - Knolker HJ FAU - Kurzchalia, Teymuras V AU - Kurzchalia TV LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Dev Cell JT - Developmental cell JID - 101120028 RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Cholestenes) RN - 0 (DAF-12 protein, C elegans) RN - 0 (Pheromones) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Sterols) RN - 0 (dafachronic acid) RN - 9035-51-2 (Cytochrome P-450 Enzyme System) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.- (DAF-9 protein, C elegans) RN - EC 2.1.1.- (Methyltransferases) RN - EC 2.1.1.- (Protein Methyltransferases) RN - EC 2.1.1.- (STRM-1 protein, C elegans) SB - IM MH - Animals MH - Caenorhabditis elegans/cytology/enzymology/*growth & development/*metabolism MH - Caenorhabditis elegans Proteins/genetics/*metabolism MH - Cholestenes/metabolism MH - Cholesterol/metabolism MH - Cytochrome P-450 Enzyme System/metabolism MH - Gene Deletion MH - Gene Expression Regulation, Developmental/drug effects MH - Larva/cytology/drug effects/growth & development/metabolism MH - Methylation/drug effects MH - Methyltransferases/genetics/*metabolism MH - Models, Biological MH - Pheromones/pharmacology MH - Protein Methyltransferases/metabolism MH - Receptors, Cytoplasmic and Nuclear/metabolism MH - Sterols/chemistry/*metabolism MH - Substrate Specificity/drug effects EDAT- 2009/06/18 09:00 MHDA- 2009/07/15 09:00 CRDT- 2009/06/18 09:00 PHST- 2008/07/13 00:00 [received] PHST- 2009/02/24 00:00 [revised] PHST- 2009/04/24 00:00 [accepted] PHST- 2009/06/18 09:00 [entrez] PHST- 2009/06/18 09:00 [pubmed] PHST- 2009/07/15 09:00 [medline] AID - S1534-5807(09)00174-9 [pii] AID - 10.1016/j.devcel.2009.04.012 [doi] PST - ppublish SO - Dev Cell. 2009 Jun;16(6):833-43. doi: 10.1016/j.devcel.2009.04.012.