[
International Worm Meeting,
2003]
In all metazoa the regulation of cell-cell-signaling is essential for development and behaviour. Neprilysins (NEP, neutral endopeptidases), transmembrane proteins belonging to the big family of zinc-metalloproteases, play a central regulatory role in these processes. In mammals, their main function is the hydrolysis of small neuropeptides at the cell surface leading to a termination of signals between neurons. In C. elegans more than 20 putative neprilysin genes are known but until now the physiological function of their corresponding proteins is unclear. Five of these neprilysins (F18A12.8, F26G1.6, T05A8.4, T16A9.4 and ZK20.6) show more than 30 % amino acid sequence identity to the mammalian neprilysin EC3.4.24.11. NEP-knockout mice show a decreased -opioid receptor density in the brain, increased aggression behaviour and altered locomotion activity. We are interested in effects on C. elegans behaviour and development caused by knockout of neprilysins. RNAi experiments were performed without detecting a change of the wild type phenotype. In parallel, a NEP deletion mutant was isolated by screening EMS-mutagenesis libraries. The knockout strain shows decreased, uncoordinated locomotion when compared to wild type. A temperature shift (from 20 to 26C) leads to a high embryonal lethality in these NEP deletion animals. We are continuing the characterisation of the deletion mutant strain and screen for additional NEP deletion mutants.