Investigating the Role of Neuropeptide Receptor 14 (NPR-14) in C. elegans Sleep

Abstract

Narcolepsy is a chronic sleep disorder that affects an estimated 1 in 2,000 people in the United States and Europe, making it one of the most prevalent sleep conditions worldwide (Longstreth et al., 2009; Silber et al., 2002). Studies in human and animal models have revealed a causative link between instances of narcolepsy and decreased orexin signaling. In Caenorhabditis elegans, a G protein-coupled receptor called neuropeptide receptor 14 (NPR-14) has been identified as a potential ortholog to the human orexin 2 receptor (OX2R). npr-14 mutants display a marked reduction in adult locomotion and mechanosensory stimulation compared to wildtype strains. The narcoleptic-like phenotype observed in npr-14 mutants, along with the proposed orthologous relationship to OX2R, suggests that npr-14 is involved in the regulation of sleep in C. elegans. This work endeavours to elucidate the role of NPR-14 in the C. elegans stress induced sleep (SIS) pathway. Epistasis experiments between NPR-14 and SIS regulators LIN-3, FLP-11, FLP-24, and DMSR-1 have revealed a potential location of NPR-14 within the SIS pathway. Data suggests that NPR-14 acts downstream of LIN-3 and FLP-24, and upstream of DMSR-1 and FLP-11 during SIS. Results from this study contribute towards successful characterization of NPR-14’s role in C. elegans sleep. A greater understanding of how NPR-14 contributes to sleep in C. elegans may provide a model system in which the pathology of narcolepsy and other fatigue-presenting conditions can be explored.