Global analysis of ligand-gated ion channel conservation across Platyhelminthes

Abstract

Ligand-gated ion channels (LGICs) are critical for neurotransmission, mediating responses to neurotransmitters and hormones, and influencing diverse physiological processes. This study identifies and classifies LGICs across Platyhelminthes, with a particular focus on parasitic neodermatans, which impact human and animal health. Using bioinformatics tools, we analyzed LGICs from 41 neodermatan species and expanded our investigation to encompass vertebrates, other invertebrates, and non-bilaterians to trace LGIC evolutionary pathways across Metazoa. We identified 2,269 putative LGICs within neodermatan species, which we classified into the cys-loop, ASIC/Deg/ENaC, iGluR, and P2X families. Our phylogenetic and clustering analyses reveal lineage-specific patterns with distinct evolutionary trajectories for each LGIC family in neodermatans compared to free-living platyhelminths and other taxa. Notably, the ASIC/Deg/ENaC family displayed the greatest degree of neodermatan-specific divergence, while cys-loop and P2X families were more conserved across taxa. To provide insight into their potential physiological roles, we analyzed LGIC expression patterns in Schistosoma mansoni, revealing widespread expression across neuronal and muscle cell types. The distribution of acid-sensing ion channels (ASICs) in both neurons and muscles suggests a role in neuromuscular signalling, while the P2X receptor (Smp_333600) exhibited sex-specific expression, potentially indicating distinct functional roles in males and females. Additionally, several cys-loop acetylcholine and GABA receptors showed differential neuronal and muscle expression, highlighting their likely contributions to cholinergic and inhibitory neurotransmission. These findings underscore the relevance of LGICs in parasite physiology, particularly in neuromuscular and sensory processes, and suggest potential targets for antiparasitic interventions.