Methylation of the sterol nucleus by STRM-1 regulates dauer larva formation in Caenorhabditis elegans

Dev Cell. 2009 Jun;16(6):833-43. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cholestenes / metabolism
  • Cholesterol / metabolism
  • Cytochrome P-450 Enzyme System / metabolism
  • 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
  • Pheromones / pharmacology
  • Protein Methyltransferases / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Sterols / chemistry
  • Sterols / metabolism*
  • Substrate Specificity / drug effects


  • Caenorhabditis elegans Proteins
  • Cholestenes
  • DAF-12 protein, C elegans
  • Pheromones
  • Receptors, Cytoplasmic and Nuclear
  • Sterols
  • dafachronic acid
  • Cytochrome P-450 Enzyme System
  • Cholesterol
  • DAF-9 protein, C elegans
  • Methyltransferases
  • Protein Methyltransferases
  • STRM-1 protein, C elegans