The cys-loop ligand-gated ion channel gene family of Brugia malayi and Trichinella spiralis: a comparison with Caenorhabditis elegans

Abstract

Nematode cys-loop ligand gated ion channels (CLGIC) mediate neurotransmission and are important targets for anthelmintics in parasitic nematodes. The CLGIC superfamily in nematodes includes ion channels gated by acetylcholine, gamma-amino butyric acid (GABA), glutamate, glycine and 5-HT. The macrocyclic lactones and the nicotinic agonists are important groups of anthelmintics that target the glutamate gated chloride channels and the nicotinic acetylcholine receptors, respectively. The model organism Caenorhabditis elegans has the most diverse families of cys-loop LGIC known in any organism. Many parasitic nematodes have homologues of C. elegans receptors but to date no genome wide investigations have been done. The genome sequencing projects of Brugia malayi (clade III) and Trichinella spiralis (clade I) have allowed us to characterise the CLGIC families in these species. Although the main groups of CLGICs targeted by anthelmintics are represented in both the nematode genomes investigated here, the CLGIC family is much smaller in B. malayi and T. spiralis, suggesting that care must be taken when using C. elegans as a model organism for distantly related nematodes.

Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi

“…A homology search revealed four possible GluCl subunits in B. malayi (16). Phylogenetic analysis and naming according to Beech et al (19) allowed us to infer that these subunits are orthologs of the GLC-2, GLC-4, AVR-14A, and AVR-14B subunits in C. elegans and other nematodes.…”

“…1073/pnas.1011983107/-/DCSupplemental. reveals only four subunits, two of them (AVR-14A and AVR-14B) related to IVM-sensitive channels (15,16).…”

The astacin metalloprotease moulting enzyme NAS-36 is required for normal cuticle ecdysis in free-living and parasitic nematodes

“…vertebrates (Möhrlen et al 2006), many of which demonstrate essential developmental functions including digestion, hatching, embryogenesis, processing of the extracellular matrix, skeleton formation and morphogenesis (Bond and Beynon, 1995). The astacin metalloproteases have also been found to have crucial developmental roles in a wide range of freeliving and parasitic nematodes, including C. elegans (Hishida et al 1996;Möhrlen et al 2003;Davis et al 2004;Novelli et al 2004;Suzuki et al 2004;Park et al 2010), O. volvulus (Borchert et al 2007), H. contortus (Gamble et al 1989;Stepek et al 2010b), A. caninum (Williamson et al 2006) and S. stercoralis (Gallego et al 2005). In general, the C. elegans astacins are associated with tissues exposed to the external environment and have diverse functions which, in part, relate to unique nematode-specific extracellular structures, such as the eggshell, the cuticular exoskeleton and the cuticular pharyngeal grinder (Park et al 2010).…”

“…Therefore, NAS-36 may be essential for cuticle ecdysis in parasitic nematodes and suggests a degree of redundancy in the C. elegans astacin family. Williamson et al (2007) indicated potential gene redundancy in proteins that belong to the Cys-loop ligand gated ion channels family, with a larger gene family in C. elegans in comparison to B. malayi and Trichinella spiralis. Another nematode astacin metalloprotease of subgroup V, NAS-34, is necessary for normal hatching of the embryo of C. elegans (Hishida et al 1996).…”

“…There are 39 individual astacin metalloproteases in the genome of C. elegans (Möhrlen et al 2003), approximately 13 in the B. malayi genome (Ghedin et al 2007) and an, as yet, unknown number in the genome of H. contortus, although this current study may suggest that there are fewer members than in the C. elegans genome. The presence of larger, redundant gene families in C. elegans compared to the parasitic nematodes, which have comparably sized genomes, is becoming a well-established feature (Ghedin et al 2007;Williamson et al 2007) and may either be due to gene expansion in C. elegans or indeed gene loss in the parasitic nematodes.…”