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C. elegans study identifies orexin-receptor homologue NPR-14 as an arousal promoter

A bioRxiv preprint from Cold Spring Harbor Laboratory characterises NPR-14, a G-protein-coupled receptor in Caenorhabditis elegans, as a promoter of arousal that suppresses sleep-like quiescence — offering a genetically tractable model for studying conserved sleep-regulatory pathways.

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Researchers have posted a preprint on bioRxiv describing their characterisation of NPR-14, a G-protein-coupled receptor in the nematode Caenorhabditis elegans that belongs to the orexin/allatotropin receptor family and has previously been proposed as a homologue of the mammalian orexin receptors.

Using loss-of-function mutants, the team demonstrates that NPR-14 promotes arousal and inhibits sleep-like quiescence: animals lacking functional NPR-14 display prolonged quiescent bouts and reduced locomotion relative to wild-type controls. Sleep-like quiescence in C. elegans is an evolutionarily conserved state considered essential for physiological homeostasis, and its dysregulation in mammals is associated with conditions including narcolepsy, which involves disrupted orexin signalling.

Because C. elegans offers a compact, fully mapped nervous system amenable to rapid genetic manipulation, findings in this model can help researchers dissect the molecular logic of neuropeptide-mediated arousal circuits. The work adds to a body of literature exploring whether NPR-14 is a functional counterpart of mammalian orexin receptors, which would make the worm a tractable system for forward-genetic screens relevant to sleep biology.

This work is a preprint and has not yet undergone peer review. Results and interpretations should be treated as preliminary until independent review and, where appropriate, replication.

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  1. Primary sourcePreprint bioRxiv (Cold Spring Harbor Laboratory) · 2026-07-25
    Characterization of NPR-14 in the Regulation of Sleep-Like Behaviour in Caenorhabditis elegans

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npr-14 orexin-receptor sleep-biology c-elegans neuropeptide-signalling model-organisms preprint
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