| Title: | Methylation of the sterol nucleus by STRM-1 regulates dauer larva formation in Caenorhabditis elegans |
| Author(s): | Hannich JT; Entchev EV; Mende F; Boytchev H; Martin R; Zagoriy V; Theumer G; Riezman I; Riezman H; Knolker HJ; Kurzchalia TV; |
| Address: | "Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany" |
| DOI: | 10.1016/j.devcel.2009.04.012 |
| ISSN/ISBN: | 1878-1551 (Electronic) 1534-5807 (Linking) |
| 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" |
| Keywords: | Animals Caenorhabditis elegans/cytology/enzymology/*growth & development/*metabolism Caenorhabditis elegans Proteins/genetics/*metabolism Cholestenes/metabolism Cholesterol/metabolism Cytochrome P-450 Enzyme System/metabolism Gene Deletion Gene Expression; |
| Notes: | "MedlineHannich, J Thomas Entchev, Eugeni V Mende, Fanny Boytchev, Hristio Martin, Rene Zagoriy, Vyacheslav Theumer, Gabriele Riezman, Isabelle Riezman, Howard Knolker, Hans-Joachim Kurzchalia, Teymuras V eng Research Support, Non-U.S. Gov't 2009/06/18 Dev Cell. 2009 Jun; 16(6):833-43. doi: 10.1016/j.devcel.2009.04.012" |
