MOLECULAR-CLONING OF A PREPROHORMONE FROM SEA-ANEMONES CONTAINING NUMEROUS COPIES OF A METAMORPHOSIS-INDUCING NEUROPEPTIDE - A LIKELY ROLE FOR DIPEPTIDYL AMINOPEPTIDASE IN NEUROPEPTIDE PRECURSOR PROCESSING

Neuropeptides are an important group of hormones mediating or modulati ng neuronal communication. Neuropeptides are especially abundant in ev olutionarily ''old'' nervous systems, such as those of cnidarians, the lowest animal group having a nervous system. Cnidarians often have a life cycle including a polyp, a medusa, and a planula larva stage. Rec ently, a neuropeptide, < Glu-Gln-Pro-Gly-Leu-Trp-NH2, has been isolate d from sea anemones that induces metamorphosis in a hydroid planula la rva to become a hydropolyp [Leitz, T., Morand, K. & Mann, M. (1994) De v. Biol. 163, 440-446]. Here, we have cloned the precursor protein for this metamorphosis-inducing neuropeptide from sea anemones. The precu rsor protein is 514-amino acid residues long and contains 10 copies of the immature, authentic neuropeptide (Gln-Gln-Pro-Gly-Leu-Trp-Gly). A ll neuropeptide copies are preceded by Xaa-Pro or Xaa-Ala sequences, s uggesting a role for dipeptidyl aminopeptidase in neuropeptide precurs or processing. In addition to these neuropeptide copies, there are 14 copies of another, closely related neuropeptide sequence (Gln-Asn-Pro- Gly-Leu-Trp-Gly). These copies are flanked by basic cleavage sites and , therefore, are likely to be released from the precursor protein. Fur thermore, there are 13 other, related neuropeptide sequences having on ly small sequence variations (the most frequent sequence: Gln-Pro-Gly- Leu-Trp-Gly, eight copies). These variants are preceded by Lys-Arg, Xa a-Ala, or Xaa-Pro sequences, and are followed by basic cleavage sites, and, therefore, are also likely to be produced from the precursor. Th us, there are at least 37 closely related neuropeptides localized on t he precursor protein, making this precursor one of the most productive preprohormones known so far. This report also shows that unusual proc essing sites are common in cnidarian preprohormones.