Biosynthesis of neuropeptides in cnidarians: evidence for unusual neuropeptide precursor processing enzymes

Summary

Evolutionarily “old” nervous systems, such as those of cnidarians, are strongly peptidergic. From a single sea anemone species, Anthopleura elegantissima, we and other collegues have recently isolated 17 different neuropeptides. Many of these neuropeptides are located in neuronal secretory vesicles and have excitatory or inhibitory actions on muscle preparations or isolated muscle cells, suggesting that they are neurotransmitters or neuromodulators. One of the sea anemone neuropeptides, <Glu-Gln-Pro-Gly-Leu-TrpNH₂ (metamorphosin A, or MMA) induces metamorphosis in a hydroid planula larva to become a hydropolyp. This shows that cnidarian neuropeptides also can be neurohormones that control developmental processes, such as growth, differentiation and pattern formation. We have cloned the precursor proteins for most of the cnidarian neuropeptides. Here, we give the precursor protein for MMA as an example. PreproMMA contains 10 copies of authentic, immature MMA (Gln-Gln-Pro-Gly-Leu-Trp-Gly) and 27 other, closely related, putative neuropeptide sequences. The 10 copies of immature MMA are preceded by the sequence Xaa-Ala-Xaa-Pro, suggesting that dipeptidyl aminopeptidase IV plays a role in the final processing of Xaa-Ala-Xaa-Pro-MMA. This illustrates that primitive nervous systems use unusual processing enzymes for the maturation of their neuropeptide precursors.