Figure 10: Schematic representation of the role of cGMP/PfPKG signalling in egress/invasion.

The present study has identified a number of cellular targets for PfPKG, which appear to map to the reported roles for cGMP and calcium signalling in egress and invasion. We describe here the PfPKG-dependent phosphorylation of a subpopulation of PfCDPK1 localized at the apical pole, which together with other calcium-dependent kinases, most notably PfCDPK5, represents an interplay between calcium and cGMP/PfPKG signalling necessary to mediate egress. Interestingly, this may also involve phosphorylation of additional proteins involved in egress, such as the recently described PfSEA1, which we demonstrate here to be a target (either direct or indirect) for PfPKG. Furthermore, the identification of a number of proteins involved in parasite invasion, particularly those associated with the actomyosin motor complex, provides a mechanistic explanation for the essential role played by PfPKG in invasion that is described in our study.