|Nachman, Ronald - Ron|
Submitted to: Journal of Comparative Neurology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/3/2004
Publication Date: 6/28/2004
Citation: Predel, R., Wegener, C., Russell, W.K., Tichy, S.E., Russell, D.H., Nachman, R.J. 2004. Peptidomics of CNS-associated neurohemal systems of adult Drosophila melanogaster: A mass spectrometric survey of peptides from individual flies. Journal of Comparative Neurology. 474:379-392. Interpretive Summary: Because of problems with the development of resistance to conventional pesticides, there is a critical need for new concepts and alternative approaches in controlling insect pests. The basic premise of this research is that neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions. New, selective control measures may be developed by designing metabolically stable mimics of these neuropeptides that actively inhibit or over-stimulate functions regulated by them, resulting in disruption of the internal environment of the insect. We report on the use of state-of-the-art analytical techniques to characterize in a species of fly the 'neurohemal peptidome', the entire collection of peptides associated with the nervous and endocrine system within a given organism. A deeper understanding of the specific structures of neuropeptides, where they are stored and released, and how these neuropeptides regulate critical processes in insects will aid in the design of strategies to disrupt feeding and survival. The work brings us one step closer to the development of practical neuropeptide-like substances that will be effective in controlling pest insects in an environmentally friendly fashion.
Technical Abstract: Neuropeptides are important messenger molecules that influence nearly all physiological processes. In insects, they can be released as neuromodulators within the central nervous system (CNS) or as neurohormones into the hemolymph. We analyzed the peptidome of neurohormonal release sites and associated secretory peptidergic neurons of adult Drosophila melanogaster. MALDI-TOF mass spectrometric analyses were performed on single organs or cell clusters from individual flies. This first peptidomic characterization in adult fruit flies revealed 32 different neuropeptides. Peptides not directly predictable from previously cloned or annotated precursor genes were sequenced by tandem mass spectrometry. These peptides turned out to be either intermediate products of neuropeptide processing or shorter versions of known peptides. We found that the peptidome of the CNS-associated neurohemal organs is tagma-specific in Drosophila. Abdominal neurohemal organs and their supplying peptidergic neurons contain the capa gene products periviscerokinins and pyrokinin-1, thoracic neurohemal organs contain FMRFamides, and the neurohemal release sites of the brain contain pyrokinin-1(2-15), pyrokinin-2, corazonin, myosuppressin, and sNPF as their major putative release products. Our results show that peptidomic approaches are well suited to study differential neuropeptide expression or posttranslational modifications in morphologically defined parts of the nervous system and in a developmental and physiological context in animals as small as Drosophila melanogaster.