|Predel, Reinhard -|
|Neupert, Susanne -|
|Crim, Joe -|
|Brown, Mark -|
|Russell, William -|
|Kahnt, Jorg -|
|Russell, David -|
Submitted to: Journal of Proteome Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 23, 2010
Publication Date: March 18, 2010
Citation: Predel, R., Neupert, S., Garczynski, S.F., Crim, J.W., Brown, M.R., Russell, W.K., Kahnt, J., Russell, D.H., Nachman, R.J. 2010. Neuropeptidomics of the mosquito Aedes aegypti. Journal of Proteome Research. 9:2006-2015. 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. Nevertheless, neuropeptides in and of themselves hold little promise as pest control agents because of susceptibility to being degraded in the target pest. Neuropeptide mimics must be designed that resist degradation by enzymes in the digestive tract and blood of pest insects and interact with the active site within agricultural pests by over-activating or blocking critical, neuropeptide-regulated life functions. The first step is to identify neuropeptide structures in specific insect pests and map sites of production and storage within the nervous system. We report on the identification of neuropeptides of a large number of classes from the central nervous system of the yellow fever mosquito, which transmits diseases to humans. In addition, storage and release sites have been mapped in the nervous systems of these insect pests. Specifically, we have used state-of-the-art analytical techniques to determine the structures of over fifty peptides from the mosquito. This work represents an important milestone and/or lead in the development of practical neuropeptide-like substances that will effectively control insect pests in an environmentally friendly fashion.
Technical Abstract: Neuropeptidomic data were collected on the mosquito Ae. aegypti which is considered the most tractable mosquito species for physiological and endocrine studies. The data were solely obtained by direct mass spectrometric profiling, including tandem fragmentation, of selected tissues from single specimens which yielded a largely complete accounting of the putative bioactive neuropeptides; truncated neuropeptides with low abundance were not counted as mature peptides. Differential processing within the CNS was detected for the CAPA-precursor and differential post-translational processing (pyroglutamate formation) was detected for AST-C and CAPA-PVK-2. For the first time in insects, we succeeded in the direct mass spectrometric profiling of midgut tissue which yielded a comprehensive and immediate overview of the peptides involved in the endocrine system of the gut. Head peptides which were earlier identified as the most abundant RFamides of Ae. aegypti, were not detected in any part of the CNS or midgut. This study provides a framework for future investigations on mosquito endocrinology and neurobiology. Given the high sequence similarity of neuropeptide precursors identified in other medically important mosquitoes, conclusions regarding the peptidome of Ae. aegypti likely are applicable to these mosquitoes.