Creation by mutagenesis of a mammalian Ca 2+ channel β subunit that confers praziquantel sensitivity to a mammalian Ca 2+ channel

Abstract

Voltage-gated Ca 2+ channel β subunits are important modulators of the pore-forming α 1 subunit. We have cloned two schistosome β subunits that confer sensitivity to the antischistosomal drug praziquantel (PZQ) to an otherwise insensitive mammalian α 1 subunit. The primary site of β subunit interaction with α 1 subunits is the beta interaction domain (BID). The BID contains two conserved serines (225, 235 in rat β2a) that constitute consensus sites for protein kinase C phosphorylation. However, these serines are absent in these schistosome β subunits. Here we show that the capability to confer PZQ sensitivity can be created in the rat β2a subunit by eliminating both serines in the BID. These results are consistent with, and should help our understanding of, the selective toxicity of PZQ.