|Poels, Jeroen -|
|Van Loy, Tom -|
|Vandersmissen, Hans -|
|Van Hiel, Boris -|
|Van Soest, Sofie -|
|Vanden Broeck, Jozef -|
Submitted to: Cellular and Molecular Life Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 27, 2010
Publication Date: June 12, 2010
Citation: Poels, J., Van Loy, T., Vandersmissen, H.P., Van Hiel, B., Van Soest, S., Nachman, R.J., Vanden Broeck, J. 2010. Myoinhibiting peptides are the ancestral ligands of the promiscuous Drosophila sex peptide receptor. Cellular and Molecular Life Sciences. 67:3511-3522. 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, these neuropeptides in and of themselves hold little promise as pest control agents because of susceptibility to being degraded in the target pest, and inability to pass through the outside skin (cuticle) and/or digestive tract. We must design neuropeptide mimics that resist degradation by enzymes in the digestive tract and blood of pest insects and interact with the active site within the agricultural pest in such a way as to either over-activate or block critical, neuropeptide-regulated life functions. We report on the discovery that neuropeptides of the ‘MIP’ class that control locomotory function also activate the active site for the ‘sex peptide’ in Drosophila melanogaster, a model for important pest flies. Sex peptide is produced by males and is involved in regulation of reproductive behaviors in female flies, and now ‘MIP’ peptides are also implicated in this important function. Structural studies have shed light on why MIP peptides interact with the active site of an entirely different class of peptide hormones. This discovery will aid in the design of neuropeptide-like compounds capable of disrupting both the locomotory and reproductive functions of these and other flies. 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: Male insects change behaviors of female partners by co-transferring accessory gland proteins (Acps) like sex peptide (SP), with their sperm. The Drosophila sex peptide receptor (SPR) is a G protein-coupled receptor expressed in the female’s nervous system and genital tract. While most Acps show a fast rate of evolution, SPRs are highly conserved in insects. We report activation of SPRs by evolutionary conserved myoinhibiting peptides (MIPs). Structural determinants in SP and MIPs responsible for this dual receptor activation are characterized. Drosophila SPR is expressed in embryonic and larval stages and in the adult male nervous system, whereas SP expression is restricted to the male reproductive system. MIP transcripts occur in male and female central nervous system, possibly acting as endogenous SPR ligands. Evolutionary consequences of the promiscuous nature of SPRs are discussed. MIPs likely function as ancestral ligands of SPRs and could place evolutionary constraints on the MIP/SP receptor class.