Function of the natalisin receptor in mating of the oriental fruit fly, Bactrocera dorsalis (Hendel) and identification of agonists/antagonists

Authors: GUI, SHUN-HUA - Chongqing University; PEI, YU-XIA - Chongqing University; XU, LI - Chongqing University; WANG, WEI-PING - Chongqing University; JIANG, HONG-BO - Chongqing University; Nachman, Ronald; KACZMAREK, KRZYSZTOF - Technical University Of Lodz; ZABROCKI, JANUSZ - Technical University Of Lodz; WANG, JIN-JUN - Chongqing University

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/16/2018
Publication Date: 2/23/2018
Citation: Gui, S., Pei, Y., Xu, L., Wang, W., Jiang, H., Nachman, R.J., Kaczmarek, K., Zabrocki, J., Wang, J. 2018. Function of the natalisin receptor in mating of the oriental fruit fly, Bactrocera dorsalis (Hendel) and identification of agonists/antagonists. PLoS One. 13(2):e0193058. https://doi.org/10.1371/journal.pone.0193058.
DOI: https://doi.org/10.1371/journal.pone.0193058

Interpretive Summary: Insect pests have developed resistance to several conventional pesticides, and new approaches are needed for pest management. Although neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions, the neuropeptides hold little promise as pest control agents because they can be degraded in the target pest. New, selective control agents may be developed by designing mimics of these neuropeptides that resist degradation and either inhibit or over-stimulate critical neuropeptide-regulated life functions. In this study, the active site for ‘natalisin’ neuropeptides was shown to regulate the frequency of mating in both males and females of the oriental fruit fly, a major agricultural pest. The research also identified novel stable mimic leads that show activity on the natalisin active site, one of which can block the action of the natural peptide hormone. The discoveries revealed in this paper will aid in the design of neuropeptide-like compounds capable of disrupting the mating functions of these agricultural pest flies.

Technical Abstract: Natalisins (NTLs) are conservative neuropeptides, which are only found in arthropods and have been documented to regulate reproductive behaviors in insect species. In our previous study, we have confirmed NTL regulates the reproductive process in an important agricultural pest, Bactrocera dorsalis (Hendel), known as the oriental fruit fly. Hence, in this paper, to further confirm the in vivo function of NTL receptor (NTLR), which is a typical G protein coupled receptor (GPCR), and assess the potential of NTLR as a pesticide target, RNA interference of NTLR mRNA was performed. We found NTLR also regulated both male and female mating frequencies in B. dorsalis adults. Moreover, we functionally characterized the B. dorsalis NTLR in a heterologous reporter system. NTLR was expressed in Chinese Hamster Ovary (CHO) cells, which were co-transfected with the aequorin reporter, and was used to measure the ligand activities. A total of 13 biostable multi-Aib analogs were tested for agonistic and antagonistic activities. Two of these NTL analogs retained some agonist activity, whereas one analog (NLFQV[Aib]DPFF[Aib]TRamide) demonstrated moderate antagonistic activity. Taken together, we have provided evidence for the important roles of NTLR in regulating both male and female mating frequencies in this fly and provide in vitro data on mimetic analogs that serves as leads for the development of agonists and antagonists to disrupt the NTL signaling pathway.