We are interested in understanding the mechanisms for neurotransmitter and neuropeptide modulation of C. elegans behavior, including locomotion, defecation, and egg laying. We previously reported that the
egl-3 gene encodes a prohormone convertase involved in proteolytic processing of pro-neuropeptides (Kass and Kaplan IWM99). We will present evidence that the
egl-21 gene encodes a carboxypeptidase E(CPE), which mediates the next enzymatic step in peptide processing, removal of C-terminal basic residues. Mutations in
egl-21 were first isolated in a screen for egg laying defective mutants, but also showed defective defecation and uncoordinated locomotion (Trent, Genetics 104: 619-647 1983). The various defects in
egl-21 mutants show differing drug sensitivity: the egg laying defect is resistant to serotonin and imipramine, while the locomotion phenotype is sensitive to both. We found that
egl-21 mutations map very close to
mec-3. The genome sequence of this region indicated that a gene very similar to vertebrate CPE mapped in this region. We found that a cosmid containing this CPE rescued the
egl-21 defecation defects. Next, we showed that two
egl-21 alleles correspond to mutations in the CPE gene. The
n576 allele alters an invariant G in a splice donor sequence whereas the
n476 allele corresponds to a 122 bp in-frame deletion. Since
egl-21 encodes the only apparent CPE in the worm genome, we would expect that the phenotype of
egl-21 mutants corresponds to a neuropeptide null phenotype. We are currently studying the role of
egl-21 CPE in modulation of several behaviors.