A Novel Biological Activity of Praziquantel Requiring Voltage-Operated Ca2+ Channel β Subunits: Subversion of Flatworm Regenerative Polarity

Abstract

This study identifies a new biological activity of the antischistosomal drug praziquantel on regenerative polarity in a species of free-living flatworm. Ablation of the bipolar regenerative phenotype evoked by PZQ via in vivo RNAi of VOCC beta subunits provides the first genetic evidence implicating a molecular target crucial for in vivo PZQ activity and supports the 'VOCC hypothesis' of PZQ efficacy. Further, in terms of regenerative biology and Ca(2+) signaling, these data highlight a novel role for voltage-operated Ca(2+) entry in regulating in vivo stem cell differentiation and regenerative patterning.