A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes.
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.
Dvorin
Jeffrey D
JD
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Martyn
Derek C
DC
Patel
Saurabh D
SD
Grimley
Joshua S
JS
Collins
Christine R
CR
Hopp
Christine S
CS
Bright
A Taylor
AT
Westenberger
Scott
S
Winzeler
Elizabeth
E
Blackman
Michael J
MJ
Baker
David A
DA
Wandless
Thomas J
TJ
Duraisingh
Manoj T
MT
D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D008024:Ligands; D052940:Merozoites / Q000201:enzymology / Q000502:physiology; D008954:Models, Biological; D009025:Morpholines / Q000378:metabolism; D010963:Plasmodium falciparum / Q000166:cytology / Q000201:enzymology / Q000254:growth & development / Q000502:physiology*; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D052939:Schizonts / Q000166:cytology / Q000201:enzymology / Q000502:physiology
C452660:4-(2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H-pyrrol-3-yl)pyridine; D002135:Calcium-Binding Proteins; D004791:Enzyme Inhibitors; D008024:Ligands; D009025:Morpholines; D015800:Protozoan Proteins; D011725:Pyridines; D011758:Pyrroles; D011993:Recombinant Fusion Proteins; C540198:Shield-1 compound; D011494:Protein Kinases; C549562:CDPK5 protein, Plasmodium falciparum; D017869:Cyclic GMP-Dependent Protein Kinases
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