1. A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes.
- Author
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Dvorin JD, Martyn DC, Patel SD, Grimley JS, Collins CR, Hopp CS, Bright AT, Westenberger S, Winzeler E, Blackman MJ, Baker DA, Wandless TJ, and Duraisingh MT
- Subjects
- Calcium-Binding Proteins chemistry, Calcium-Binding Proteins genetics, Cyclic GMP-Dependent Protein Kinases antagonists & inhibitors, Cyclic GMP-Dependent Protein Kinases metabolism, Enzyme Inhibitors pharmacology, Host-Parasite Interactions, Humans, Ligands, Merozoites enzymology, Merozoites physiology, Models, Biological, Morpholines metabolism, Plasmodium falciparum cytology, Plasmodium falciparum enzymology, Plasmodium falciparum growth & development, Protein Kinases chemistry, Protein Kinases genetics, Protozoan Proteins chemistry, Protozoan Proteins genetics, Pyridines pharmacology, Pyrroles pharmacology, Recombinant Fusion Proteins chemistry, Recombinant Fusion Proteins metabolism, Schizonts cytology, Schizonts enzymology, Schizonts physiology, Calcium-Binding Proteins metabolism, Erythrocytes parasitology, Plasmodium falciparum physiology, Protein Kinases metabolism, Protozoan Proteins metabolism
- Abstract
Clinical malaria is associated with the proliferation of Plasmodium parasites in human erythrocytes. The coordinated processes of parasite egress from and invasion into erythrocytes are rapid and tightly regulated. We have found that the plant-like calcium-dependent protein kinase PfCDPK5, which is expressed in invasive merozoite forms of Plasmodium falciparum, was critical for egress. Parasites deficient in PfCDPK5 arrested as mature schizonts with intact membranes, despite normal maturation of egress proteases and invasion ligands. Merozoites physically released from stalled schizonts were capable of invading new erythrocytes, separating the pathways of egress and invasion. The arrest was downstream of cyclic guanosine monophosphate-dependent protein kinase (PfPKG) function and independent of protease processing. Thus, PfCDPK5 plays an essential role during the blood stage of malaria replication.
- Published
- 2010
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