Caenorhabditis elegans Neprilysin NEP-1: an Effector of Locomotion and Pharyngeal Pumping

The control of signal peptide activity by cell surface proteases is one of the main factors that regulate the development and behaviour of organisms. In mammals, neprilysins (NEPs) are known to play a key role in these processes and their inactivation can initiate cellular disorganisation, which in turn may lead to prostate cancer or Hirschsprung disease. Although the proteome of the nematode Caenorhabditis elegans has been intensively studied, very little is known about the function of neprilysins. ZK20.6 (NEP-1), the C. elegans protein with highest identity to mammalian neprilysins, is a 753 amino acid residue protein that displays all neprilysin-typical characteristics, including a short intracellular domain, a transmembrane domain and a long extracellular active domain. Here we show that the expression pattern of nep-1 is limited to pharyngeal cells and a single head neuron. Compared to wild-type, the locomotion of nep-1 knockout animals is significantly impaired, a phenotype that can be rescued by the extrachromosomal re-introduction of nep-1. This suggests that this enzyme plays an important role in the regulation of nematode locomotion. Finally, electrophysiological recording of the pharyngeal activity showed a high sensitivity of the nep-1 pharynx to serotonin (5-HT) and to the neuropeptide AF1 (C. elegans FLP-8), indicating that NEP-1 is a central component that controls the neuronal innervation of pharyngeal pumping in C. elegans.