Neuropeptides modulate most behaviors, but much still remains to be learned about neuropeptide processing, trafficking and release. In C. elegans, the monoamine-dependent release of neuropeptides from the two ASI sensory neurons modulates a host of key locomotory behaviors, including aversive responses initiated by the two ASH sensory neurons. For example, ASI neuropeptides encoded by the
nlp-1, -14 and -18 genes are required for the tyramine (TA) and TYRA-3 dependent inhibition of food-stimulated aversive response to 30% 1-octanol, and ASI neuropeptides encoded by
nlp-6, -7 and -9 are required for the octopamine (OA) and SER-6 mediated inhibition of aversive response to 100% 1-octanol (Hapiak et al., 2013; Mills et al., 2012). In the present study, we have demonstrated that ASI neuropeptide preproproteins selectively involved in TA inhibition have similar, but remarked different, prosequences from neuropeptide preproproteins selectively involved in OA inhibition, suggesting that that individual ASI-expressed Gaq-coupled monoamine receptors (TYRA-3 and SER-6) have the potential to selectively stimulate the release of subsets of ASI neuropeptides. Although starvation and TA stimulate the expression of
nlp-14, based on RT-PCR, TA dramatically decreases the ASI expression of
nlp-14::gfp, supporting our hypothesis that TA stimulates the release of
nlp-14 encoded peptides from the ASIs. Importantly, OA has no effect on ASI
nlp-14::gfp expression and TA has no effect on
nlp-14::gfp expression in
tyra-3 null animals. These studies are continuing to examine the subcellular localization of each of the ASI-expressed neuropeptides and, more importantly, the role of the unique subsets of presequences on selective localization and peptide release, using chimeric neuropeptide constructs.