Sleep behavior in C. elegans occurs in association with larval molts during the four lethargus stages. Neuropeptides are small centrally secreted signaling molecules which play a central role during the regulation of sleep in mammals and flies (Crocker and Sehgal, 2010). However, roles for neuropeptide signaling during C. elegans sleep regulation are just beginning to be identified. We have found that
nlp-22 regulates sleep during lethargus and has both structural and functional similarities with the human neuropeptide neuromedin S (NMS). NMS is an anorexigenic neuropeptide, which shows a circadian pattern of expression and is expressed in a small subset of neurons in the brain, specifically in the superchiasmatic nucleus, a master circadian regulatory region (Ida et al, 2005; Mori et al, 2005). Both NMS and
nlp-22 have a FRP motif at or near their C-terminus. Simliar to NMS,
nlp-22 over-expression during normally active stages causes locomotion and feeding cessation.
nlp-22 mRNA shows cyclical expression in synchrony with the molting/lethargus cycle. NLP-22 signals downstream of LIN-42/PER. We find that
nlp-22 is expressed in a single pair of head interneurons, the RIAs. In addition, we find that reduction of
nlp-22 function results in reduced sleep during lethargus. The similar structure, relationship to a PER/LIN-42 based clock, restricted nature of expression and anorexigenic effects of NLP-22 and NMS, suggest that FRP neuropeptides serve an ancient role in the regulation of feeding and sleep.