Regulation of neuropeptide stoichiometry in neurosecretory cells

Peptidergic neurons and neurosecretory cells often contain multiple peptides, where they may be present in characteristic ratios. In this article, we describe how a set of five colocalized and coreleased peptides, two adipokinetic hormones (AKH I and AKH II), and three dimeric peptides (APRP 1, 2, and 3) are synthesized by the neurosecretory cells of the corpora cardiaca of the locust Schistocerca gregaria. We show that the five peptides are produced from two prohormones called pro-AKH I, or A-chain, and pro-AKH II, or B-chain. The amino acid sequences as determined by direct protein sequencing are given for both. Prior to processing, the two prohormones form the three possible dimers by the oxidation of the single cysteine residues found in each. The dimers, not the prohormones, are the direct precursors of the peptides. The dimeric precursors are called P1 (A-A), P2 (A-B), and P3 (B-B). Processing results in the generation of the two AKH peptides and the three dimers called adipokinetic hormone precursor-related peptides, or APRPs. Throughout postembryonic development, we show that the ratios of the AKHs and APRPs change dramatically and systematically. We show that these changes can be explained by the differential regulation of the synthesis of the two prohormones and their random association into dimers that are then completely processed. Regulation of peptide stoichiometry may expand the potential information content of the signals generated by multipeptide-producing neurons.