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

J Thomas Hannich; Eugeni V Entchev; Fanny Mende; Hristio Boytchev; René Martin; Vyacheslav Zagoriy; Gabriele Theumer; Isabelle Riezman; Howard Riezman; Hans-Joachim Knölker; Teymuras V Kurzchalia

doi:10.1016/j.devcel.2009.04.012

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.

Authors

J Thomas Hannich¹, Eugeni V Entchev, Fanny Mende, Hristio Boytchev, René Martin, Vyacheslav Zagoriy, Gabriele Theumer, Isabelle Riezman, Howard Riezman, Hans-Joachim Knölker, Teymuras V Kurzchalia

Affiliation

¹ Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.

PMID: 19531354
DOI: 10.1016/j.devcel.2009.04.012

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.

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

Substances

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