Mining Nematode Genomes for Endocannabinoid Receptors

Abstract

The endocannabinoids N-arachidonoyl-ethanolamine (AEA; anandamide) and 2-arachidonoylglycerol (2-AG) are significant components of the endocannabinoid (EC) system. Cannabinoid receptors mediate EC function, and they modulate biological processes in pain management, behavioural control, appetite and memory. Cannabinoid receptor type 1 (CB1) and Cannabinoid receptor type 2 (CB2) are the two major EC receptors in mammals. NPR-19, like human CB1, is the CB receptor in nematodes. Transient receptor potential (TRP) channels are known as non-EC receptors, mostly augmented in the central nervous system and involved in behavioural control pathways along with the endocannabinoid receptors in Caenorhabditis Elegans and other invertebrates and vertebrates. CBs can activate both endocannabinoid and TRP channel receptors. In C. elegans, the 2-AG cannabinoid directly activates the TRP-like channels such as TRPN in dopaminergic and TRPV1 in serotonergic neurons. TRP4 encodes for the TRPN channel, and OSM-9 encodes for TRPV1. In the present study, we comprehensively investigated the pattern of occurrence of two (TRP4 and OSM-9) endocannabinoids’ pathway receptors proteins in 139 nematodes species. We extracted the homologs of these enzymes from WormBase. Later, using HMMer-based profiles and WormBase ParaSite BLASTp, we shortlisted and validated genes for these receptors in nematodes species. In the present study, we investigate the contributions of two receptors (TRPV1 and TRPN; encoded by TRP-4 and OSM-9 genes, respectively) in the regulation of the endocannabinoid signalling pathway of nematodes. Transient receptor potential TRPN involved in the locomotion inhibition pathway was found in 67 nematodes. The TRPV1 signalling pathway is involved in serotonergic neuron release found in 65 nematode species. We did not find the gene for OSM -9 and in the 12 species gene for TRP-4 in the 44-nematode species. For species with no TRP-4 and OSM-9 genes, we can say that they may have other similar alternative pathways for sensory modulation and decision-making behaviour.