Table 2.
Ion channel and receptor genes encoding anthelmintic targets in C. elegans and parasitic nematodes. Nematodes contain a plethora of genes encoding receptors and ion channels and it is beyond the scope of this article to provide a full comparison between the species. Shown here are the C. elegans genes that have been shown to encode components of anthelmintic drug targets, along with the equivalent target genes in H. contortus and, where available, selected other parasitic species. Members of the gene families that have not been shown to encode drug targets (e.g. the predicted GluCl gene glc-4) have been excluded. Older gene names, especially for H. contortus, used in the literature are shown in brackets.
| Drug class | Target | C. elegans genes | H. contortus genes | Other parasites |
|---|---|---|---|---|
| Macrocyclic lactones | GluCl | glc-1 | Hco-glc-2b (HG4) | avr-14 is present in all species examined. glc-2 is present in clades 3, 4 and 5. glc-3 is present in clades 4 and 5 |
| glc-2 (when co-expressed with glc-1) | Hco-glc-3b | |||
| glc-3 | Hco-avr-14b (HG3, GluClα3B) | |||
| avr-14ba (gbr-2b) | Hco-glc-5 (GluCla, HG5) | |||
| avr-15 | Hco-glc-6b | |||
| Piperazine | GABA receptors | unc-49 | Hco-unc-49 | unc-49 is widely conserved in nematodes |
| Imidazothiazoles, tetrahydropyrimidine, tribendimidine, spiroindoles | nAChR | lev-1 | Hco-acr-8 | acr-8, unc-29, unc-38 and unc-63 are widely conserved |
| lev-8 | Hco-lev-1c | |||
| unc-29 | Hco-unc-29d | |||
| unc-38 | Hco-unc-38 | |||
| unc-63 | Hco-unc-63 | |||
| AADs | Choline receptors | acr-23 | Hco-mptl-1e | acr-23/mptl-1is absent from clade 1, 3 and 4 parasites |
| deg-3 | Hco-deg-3 | |||
| des-2 | Hco-deg-2 | |||
| Cyclic depsipeptides | Potassium channels | slo-1 | Hco-slo-1 | Widely conserved |
| Cyclic depsipeptides | Latrophilin receptors | lat-1 | Hco-lat-1 (Hc-110R) | Widely conserved |
The avr-14 gene is alternatively spliced to give two subunits, AVR-14A and AVR-14B. To date, only AVR-14B has been shown to form a ML target.
These genes have not been formally shown to encode components of an ML-sensitive receptor.
Hco-lev-1 encodes a nAChR subunit that lacks an N-terminal signal peptide and has not been shown to contribute to a functional channel or drug target.
Hco-unc-29 has undergone at least two rounds of gene duplication, resulting in four genes, Hco-unc-29.1 to Hco-unc-29.4.
Hco-mptl-1 has not been formally shown to encode part of a monepantel-sensitive receptor.