Parasite ligands, perhaps TCA cycle intermediates generated during periods of high parasite replication, activate host GPCRs on the PV membrane and initiate a signaling cascade through host Gαq. PKC-mediated phosphorylation liberates adducin from the host cell cytoskeleton, activating the mechanosensitive plasma membrane cation channel TRPC6. CaMKII-activation following Ca2+ influx mediates phosphorylation of cytoskeletal substrates, which, upon rapid influx of Ca2+ from the extracellular media, are proteolyzed by calpain to allow for cytoskeletal dissolution and parasite release. Also see Figure S5.