Schistosome transient receptor potential melastatin channel (SmTRPM) (SmTRPM)

Schistosome transient receptor potential melastatin (TRPM) channels, particularly the SmTRPM isoform, are essential ion channels in the parasitic flatworms that cause schistosomiasis. These channels are non-selective cation channels with high calcium permeability, playing a fundamental role in the parasite's neuromuscular regulation and the structural integrity of its tegument (Park et al., 2019, Science). For over 40 years, the drug praziquantel has been the primary treatment for schistosomiasis, but its molecular target remained elusive until SmTRPM was identified as its receptor. Praziquantel functions by binding to a specific pocket in the channel's voltage-sensor-like domain, acting as an allosteric activator that forces the channel into an open state (Le et al., 2021, Science). This activation causes a massive influx of calcium, leading to immediate muscle contraction, paralysis, and tegumental vacuolization. The resulting damage to the parasite's surface exposes it to the host's immune system, which ultimately leads to parasite clearance. Because SmTRPM is phylogenetically distinct from human TRPM channels, it serves as a highly specific and effective target for anthelmintic therapy with a high therapeutic index.

Other names

SmTRPMSmTRPM-PZQSchistosoma mansoni TRPM channelPraziquantel-sensitive TRPM channel

Praziquantel acts as a potent allosteric activator of the SmTRPM channel, inducing a rapid and sustained influx of calcium ions into the parasite (Park et al., 2019, Science; Le et al., 2021, Science).