Journal of Neuroscience, Vol 11, 3246-3256, Copyright © 1991 by Society for Neuroscience
Regulation of neuropeptide stoichiometry in neurosecretory cells
S Hekimi, J Fischer-Lougheed and M O'Shea
Interdisciplinary Research Centre for Neuroscience, School of Biological Sciences, University of Sussex, Brighton, England.
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.