Conserved roles for peptidases in the processing of invertebrate neuropeptides

Invertebrates use a wide range of peptides as transmitters and hormones to regulate complex behaviour, physiology and development. These animals, espe cially those that are amenable to genetic study and are the subject of geno me-sequencing projects, provide powerful model systems for understanding th e functions of peptidases in controlling the bioactivity of peptides. Nepri lysin, a zinc metallopeptidase and a key enzyme in the metabolism of mammal ian peptides, is also implicated in the inactivation of peptides at synapse s and of circulating peptide hormones in insects and nematodes. A family of neprilysin-like genes are present in the genomes of both Drosophila metano gaster and Caenorhabditis elegans; in C. elegans it seems that individual f amily members have evolved to take on different physiological functions, be cause they are expressed in a tissue-specific manner. Angiotensin I-convert ing enzymes (peptidyl dipeptidase A, angiotensin-converting enzyme) are ano ther group of zinc metallopeptidases found in some invertebrates that lack angiotensin peptides. In D. melanogaster there are two functional angiotens in-converting enzymes that are essential for normal development. One of the se (Acer) is expressed in the embryonic heart, whereas the second enzyme (A nce) is expressed in several tissues at different stages of the life cycle. The accumulation of Ance within secretory vesicles of some peptide-synthes izing cells suggests a role for the enzyme in the intracellular processing of insect peptides. Ance is very efficient at cleaving pairs of basic resid ues from the C-terminus of partly processed peptides, suggesting a novel ro le for the enzyme in prohormone processing. Invertebrates will continue to provide insights into the evolutionarily conserved functions of known pepti dases and of those additional family members that are expected to be identi fied in the future from genome-sequencing projects.