Schistosome TRP channels: An appraisal

Abstract

Ion channels underlie electrical excitability in cells and are essential for a variety of functions, most notably neuromuscular and sensory activity. They are also validated targets for a preponderance of approved anthelmintic compounds. Transient receptor potential (TRP) channels constitute an ion channel superfamily whose members play important roles in sensory signaling, regulation of ion homeostasis, organellar trafficking, and other key cellular and organismal activities. Unlike most other ion channels, TRP channels are often polymodal, gated by a variety of mechanisms. Furthermore, TRP channels fall into several classes or subtypes based on sequence and structure. Until recently, there had been very little investigation of the properties and functions of TRP channels from parasitic helminths, including schistosomes, but that situation has changed in the past few years. Indeed, it is now clear that at least some schistosome TRP channels exhibit unusual pharmacological properties, and, intriguingly, both a mammalian and a schistosome TRP channel are activated by praziquantel, the current antischistosomal drug of choice. With the latest release of the Schistosoma mansoni genome database, several changes in predicted TRP channel sequences appeared, some of which were significant. This review updates and reassesses the TRP channel repertoire in S. mansoni, examines recent findings regarding these potential therapeutic targets, and provides guideposts for some of the physiological functions that may be mediated by these channels in schistosomes.

Keywords: Capsaicin; Ion channels; Praziquantel; Schistosoma; Schistosomiasis; TRP channels; TRPA1; TRPV1.

Graphical abstract

Fig. 1

Phylogenetic tree of predicted S. mansoni TRP channels. Neighbor-joining tree of predicted S. mansoni TRP channel protein sequences, shown with closest human TRP channel subtype (color coded by subfamily). As in previous analyses, there are no predicted TRPV-like sequences. Smp_246790 (Sm.TRPM_PZQ) clusters more closely with TRPM1 channels, although it has been shown to be homologous to TRPM2 channels (Park et al., 2019), highlighting the uncertainty of the subtype classifications. For the sake of simplicity, only a single predicted splice variant is shown for genes predicted to contain multiple variants (see Table 1). Tree was derived using alignment and tree building software as implemented in MEGA X (Kumar et al., 2018). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)