Fig. 6.

Regulation of invasion by PfCDPK1 and PfPKA. a The invasion of PKA-R-GFP schizonts in the absence (squares) or presence (triangles) of 8Br-cAMP was assessed by counting the number of rings and schizonts on Giemsa smears after indicated time as described above. A representative of three independent experiments is shown. b Shld-1 was withdrawn from the parasites and invasion assays were performed using schizonts as described above. In one set of experiments PKI was added for 3 h before addition of fresh RBCs for invasion. The number of rings formed were counted from Giemsa stained thin blood smears, which reflected successful invasion. Data represents % invasion with respect to Shld-1 treated parasites (100%) (Mean±s.e.m., n=2 *, ANOVA, p<0.05, **p>NS). c Model of PfCDPK1 mediated signaling in malaria parasite: PLC-mediated calcium release results in the activation of PfCDPK1 (Pushkar Sharma, unpublished results), which triggers phosphorylation of key substrates like IMC-glideosome proteins that include IMC1g, IMC1c, and PfGAP45. PfCDPK1 facilitates the activation of PfPKA-C by promoting its dissociation from PfPKA-R. PfCDPK1 may be turned off in the parasite via a negative feedback loop regulated by PfPKA. These events and the regulation of exocytosis of EBA-175 by PfCDPK1 signaling may contribute to the process of invasion