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

• Published in: Developmental cell Vol. 16; no. 6; pp. 833 - 843
• Main Authors: Hannich, J. Thomas, Entchev, Eugeni V., Mende, Fanny, Boytchev, Hristio, Martin, René, Zagoriy, Vyacheslav, Theumer, Gabriele, Riezman, Isabelle, Riezman, Howard, Knölker, Hans-Joachim, Kurzchalia, Teymuras V.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 01.06.2009; Cell Press
• Subjects: Animals; Biological and medical sciences; Caenorhabditis elegans - cytology; Caenorhabditis elegans - enzymology; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cholestenes - metabolism; Cholesterol - metabolism; Cytochrome P-450 Enzyme System - metabolism; DEVBIO; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Expression Regulation, Developmental - drug effects; Larva - cytology; Larva - drug effects; Larva - growth & development; Larva - metabolism; Methylation - drug effects; Methyltransferases - genetics; Methyltransferases - metabolism; Models, Biological; Molecular and cellular biology; Pheromones - pharmacology; Protein Methyltransferases - metabolism; Receptors, Cytoplasmic and Nuclear - metabolism; Sterols - chemistry; Sterols - metabolism; Substrate Specificity - drug effects; DEVBIO; Caenorhabditis elegans; Nucleus; Regulation(control); Larva; Helmintha; Development; Nemathelminthia; Invertebrata; Methylation; Nematoda
• ISSN: 1534-5807; 1878-1551; 1878-1551
• 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.