A G-protein coupled receptor is involved in the regulation of sleep and metabolism

Abstract

Sleep is an evolutionary conserved behaviour which in most species is essential for survival. However, the mechanisms involved in the genetic regulation of sleep remain poorly understood. C. elegans exhibit a number of sleep-like behaviours: a) lethargus which is a developmental period between moults, b) satiety which occurs after feeding and c) after long durations of thrashing in liquid media. We have isolated a C. elegans G-protein coupled receptor, named NPR-14,that is most similar to the human orexin receptor 2 and is involved in the above behaviours and functions through a protein kinase G - dependent and independent pathways. NPR-14 works together with other signalling pathways that have been implicated in sleep regulation including Notch, GABA, and insulin signalling. A null mutation in npr-14 results in anachronistic quiescence especially in the presence of food. It also results in egg-laying defects, episodic swimming behaviour, asynchronicity during development and despite feeding less these mutants appear to accumulate more fat than N2 worms.