The Neuropeptides FLP-2 and PDF-1 Act in Concert To Arouse Caenorhabditis elegans Locomotion

Genetics. 2016 Nov;204(3):1151-1159. doi: 10.1534/genetics.116.192898. Epub 2016 Aug 31.


During larval molts, Caenorhabditis elegans exhibits a sleep-like state (termed lethargus) that is characterized by the absence of feeding and profound locomotion quiescence. The rhythmic pattern of locomotion quiescence and arousal linked to the molting cycle is mediated by reciprocal changes in sensory responsiveness, whereby arousal is associated with increased responsiveness. Sensory neurons arouse locomotion via release of a neuropeptide (PDF-1) and glutamate. Here we identify a second arousing neuropeptide (FLP-2). We show that FLP-2 acts via an orexin-like receptor (FRPR-18), and that FLP-2 and PDF-1 secretion are regulated by reciprocal positive feedback. These results suggest that the aroused behavioral state is stabilized by positive feedback between two neuropeptides.

Keywords: Caenorhabditis elegans; PDF; lethargus; orexin; sleep.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Arousal*
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Feedback, Physiological
  • Glutamic Acid / metabolism
  • Locomotion*
  • Neuropeptides / genetics*
  • Neuropeptides / metabolism
  • Orexin Receptors / genetics
  • Orexin Receptors / metabolism
  • Sensory Receptor Cells / metabolism
  • Sensory Receptor Cells / physiology


  • Caenorhabditis elegans Proteins
  • Flp-2 protein, C elegans
  • Neuropeptides
  • Orexin Receptors
  • PDF protein, C elegans
  • Glutamic Acid