2-arachidonoyl glycerol in Caenorhabditis elegans dauer diapause regulation.

GALLES, C; PORTA, E.; PREZ, G. M.; DE MENDOZA, D.

Cordoba

Congreso; Congreso SAIB 2016; 2016

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

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. 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). In order to focus on the PUFA-depletion effect we constructed a daf-7;fat-3 double mutant, which is deficient in the production of 2-AG, and we found that this strain has a higher percentage of dauer formation than daf-7. Moreover, this strain can also overcome dauer arrest by 2-AG supplementation. We also show, using the HPLC-MS/MS technique, that this eCB is indeed synthesized by wild type worms, but not by the double mutant daf7;fat-3. 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.