The Orcokinin Neuropeptide NLP-14 Regulates Sleep in C. elegans

Caenorhabditis elegans displays two distinct sleep states: Developmentally timed sleep (DTS), which occurs during a life stage called lethargus (Raizen et al., 2008) and stress induced sleep (SIS), which occurs following exposure to environmental stress that damages cells. Both sleep states have been shown to be regulated by distinct neuropeptide signaling pathways. We have identified a new neuropeptide pathway that regulates SIS, neuropeptide‐like protein‐14 (NLP‐14). NLP‐14 shares sequence similarities (~69%) with a class of neuropeptides in arthropods called orcokinins (Nathoo et al., 2001), which are highly conserved within Ecdysozoans. In cockroaches, injection of exogenous orcokinin into the accessory medulla, a circadian pacemaker in the brain, results in a circadian phase shift (Hofer and Homberg, 2006). Interestingly, we have found that ectopic over‐expression of nlp‐14 during adulthood induces behavioral quiescence which resembles sleep. Specifically, when nlp‐14 over‐expression is induced under the control of a heat shock promoter, animals become quiescent for locomotion and show prolonged defecation cycles. Additionally, we find that nlp‐14 ( tm1880 ) reduction in function mutants display decreased SIS phenotype. Introduction of NLP‐14:GFP transgenes into this background rescues the SIS defects. The tm1880 allele eliminates 7 of the 12 encoded peptides in the NLP‐14 protein, leaving 5 peptides (NLP‐14‐2(2), NLP‐14‐4(2) and NLP‐14‐5(2)). We are currently attempting to remove the remaining peptides one at a time using the CRISPR‐cas9 system. Support or Funding Information John P. McNulty Scholars Program This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .