Abstract
Ticks and tick-borne diseases have a major impact on human and animal health worldwide. Current control strategies rely heavily on the use of chemical acaricides, most of which target the CNS and with increasing resistance, new drugs are urgently needed. Nicotinic acetylcholine receptors (nAChRs) are targets of highly successful insecticides. We isolated a full-length nAChR α subunit from a normalised cDNA library from the synganglion (brain) of the brown dog tick, Rhipicephalus sanguineus. Phylogenetic analysis has shown this R. sanguineus nAChR to be most similar to the insect α1 nAChR group and has been named Rsanα1. Rsanα1 is distributed in multiple tick tissues and is present across all life-stages. When expressed in Xenopus laevis oocytes Rsanα1 failed to function as a homomer, with and without the addition of either Caenorhabditis elegans resistance-to-cholinesterase (RIC)-3 or X. laevis RIC-3. When co-expressed with chicken β2 nAChR, Rsanα1 evoked concentration-dependent, inward currents in response to acetylcholine (ACh) and showed sensitivity to nicotine (100μM) and choline (100μM). Rsanα1/β2 was insensitive to both imidacloprid (100μM) and spinosad (100μM). The unreliable expression of Rsanα1 in vitro suggests that additional subunits or chaperone proteins may be required for more robust expression. This study enhances our understanding of nAChRs in arachnids and may provide a basis for further studies on the interaction of compounds with the tick nAChR as part of a discovery process for novel acaricides.
Highlights
Ticks are by far the most economically important ectoparasite of global livestock production and are important vectors of human diseases and animal diseases (Jongejan and Uilenberg, 2004)
Untranslated region (UTR) of 317 bp with a poly A tail. This sequence possesses features typical of nicotinic acetylcholine receptors (nAChRs) subunits including an N-terminal signal peptide, an extracellular N-terminal domain with loops A–F which are involved in ligand binding, a cysteine loop which consists of two disulphide bond-forming cysteines separated by 13 amino acid residues, four transmembrane domains (TM1–TM4) and a large, highly variable intracellular loop between TM3 and TM4 (Fig. 1)
Here nested-PCR has shown that R. sanguineus a1 (Rsana1) was not solely restricted to the synganglion but was present in both the Malpighian tubules and oviduct
Summary
Ticks are by far the most economically important ectoparasite of global livestock production and are important vectors of human diseases (such as tick-borne encephalitis, Lyme borreliosis) and animal diseases (including babesiosis and theileriosis) (Jongejan and Uilenberg, 2004). There is increasing resistance to every available acaricide, necessitating the urgent development of new treatments (George et al, 2004). Most existing acaricides target the tick nervous system. The cholinergic system of the tick (see Lees and Bowman, 2007) has been validated as an acaricidal target ever since tobacco extracts containing nicotine were used as an ectoparasiticide, suggesting evidence for the presence of nicotinic acetylcholine receptors (nAChRs) in the tick (Meinke, 2001). The spinosyn insecticides which target nAChRs (Geng et al, 2013) have been shown to be effective acaricides against ticks known to be pyrethroid- and organophosphate-resistant (Miller et al, 2013). The nAChRs have been validated as viable targets for acaricide development
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