Mechanistic basis of endocannabinoid signaling in Caenorhabditis elegans
Gastón Matías Prez
Max Planck Institute
Polyunsaturated fatty acids (PUFAs) and branched-chain fatty acids (BCFAs) are important membrane components and precursors of signaling molecules. To investigate the role that PUFAs and BCFAs play in C. elegans dauer diapause, we suppressed the biosynthesis of these fatty acids by using RNA interference against let-767, a major 3-ketoacyl-CoA reductase, in dauer constitutive TGF-β mutants at 20°C (the semi-permissive growth temperature). We found that let-767 RNAi enhances the formation of dauers in daf-7(e1372) animals and this arrest can be overcome by feeding the animals with 2-arachydonoylglycerol (2-AG), an important endocannabinoid (eCB) involved in several aspects of mammalian physiology and pathology. Moreover, we found that 2-AG exerts its effect in a dose-dependent manner. We also show, using HPLC-MS technique, that this endocannabinoid is indeed synthesized by wild type worms. These results indicate that 2-AG represents a signal that coordinates the status of long-chain fatty acid synthesis with metabolic changes that ultimately determine the decision between diapause and reproduction in C. elegans.