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Title: Functional comparison of two evolutionary conserved insect neurokinin-like receptors

item LOY, TOM
item Nachman, Ronald

Submitted to: Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/30/2006
Publication Date: 1/15/2007
Citation: Poels, J., Verlinden, H., Fichna, J., Loy, T.V., Franssens, V., Studzian, K., Janecka, A., Nachman, R.J., Broeck, J.V. 2007. Functional comparison of two evolutionary conserved insect neurokinin-like receptors. Peptides. 28:103-108.

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 or medical pests by over-activating or blocking critical, neuropeptide-regulated life functions. We report on a comparative study of two closely related ‘active sites’ for the insectatachykinin neuropeptide class, implicated in the regulation of water balance and digestion in insects. The results suggest that the two active sites feature different mechanisms of recognizing the structure of this neuropeptide class, potentially leading to different outcomes in the regulation of these life functions. A deeper understanding of structural requirements for neuropeptide action in insects will aid in the design of neuropeptide mimics capable of interfering with critical life functions in pest insects. This work represents an important milestone and lead in the development of practical neuropeptide-like substances that will effectively control insect pests in an environmentally friendly fashion.

Technical Abstract: Tachykinins are multifunctional neuropeptides that have been identified in vertebrates as well as invertebrates. The C-terminal FXGXRa-motif constitutes the consensus active core region of invertebrate tachykinins. In Drosophila, two putative G protein-coupled tachykinin receptors have been cloned; DTKR and NKD. This study focuses on the functional characterization of DTKR, the Drosophila ortholog of the stable fly’s tachykinin receptor (STKR). Tachykinins that contain an alanine residue instead of the highly conserved glycine (FXAXRa), display partial agonism on STKR-mediated Ca2+-responses, but not on cAMP-responses. STKR therefore seems to differentiate between a number of tachykinins. Gly- and Ala-containing tachykinins are both encoded in the Drosophila tachykinin precursor, thus raising the question whether DTKR can also distinguish these two tachykinin types. DTKR was activated by all Drosophila tachykinins and inhibited by tachykinin antagonists. Ala-containing analogs did not produce the remarkable activation behavior that was previously observed with STKR, suggesting different mechanisms of discerning ligands and/or activating effector pathways for STKR and DTKR.