A neuronal amine-gated chloride channel governs satiety in C. elegans

BLANCO MG; RAYES D; VEUTHEY T; DE ROSA MJ

Montevideo

Congreso; First Latin American Worm Meeting; 2017

Instituto Pasteur Montevideo

Food intake is a conserved behavior thatdepends on molecules that communicate the animal nutritional status to thebrain. A key process in apettite control is satiety which implies a specificsequence of behaviors: completion of food, reduced locomotion and sleep. Thishas also been described in C elegans,as these animals become quiescent by stopping feeding and moving after achievingsatiation. Nevertheless, the neural circuit and the molecular basis of satietyin this animal are poorly understood.  Amphetamine is a well known anorexigenicdrug that has been used  for obesitytreatments in humans. In C.elegans, itactivates LGC-55, an amine-gated chloride channel. We found that lgc-55 null mutants deplete their food about40% faster than wild-type controls. This is due to an increased food intake perworm in the mutants, as the number of offsprings and the growth rates do notexhibit significant differences compared to that of wild-type worms. Strikingly, quiescence experiments, an assaythat evaluate satiety in worms, revealed that the fraction of satiated worms inthe mutant strain is 2.5-fold lower. Our results suggest that theamphetamine-sensitive receptor LGC-55 is essential for satiety in C.elegans. Amine-gated inhibitorysignaling have been also evidenced in mammals and LGC-55 exhibits 35-45 %identity with human orphans receptors. This study could contribute to theelucidation of a conserved mechanism of food intake regulation throughout theanimal kingdom.