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Science 328 (5980): 910-912

Copyright © 2010 by the American Association for the Advancement of Science

A Plant-Like Kinase in Plasmodium falciparum Regulates Parasite Egress from Erythrocytes

Jeffrey D. Dvorin,1,2 Derek C. Martyn,4 Saurabh D. Patel,1,3 Joshua S. Grimley,5,* Christine R. Collins,6 Christine S. Hopp,7 A. Taylor Bright,8 Scott Westenberger,8,{dagger} Elizabeth Winzeler,8,9 Michael J. Blackman,6 David A. Baker,7 Thomas J. Wandless,5 Manoj T. Duraisingh1,{ddagger}

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.

1 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
2 Division of Infectious Diseases, Children’s Hospital Boston, Boston, MA 02115, USA.
3 Division of Gastroenterology, Children’s Hospital Boston, Boston, MA 02115, USA.
4 The Broad Institute, Cambridge, MA 02142, USA.
5 Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
6 Division of Parasitology, MRC National Institute for Medical Research, London NW7 1AA, UK.
7 London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
8 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
9 Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.

* Present address: Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.

{dagger} Present address: Illumina, Inc., San Diego, CA 92121, USA.

{ddagger} To whom correspondence should be addressed. E-mail: mduraisi{at}hsph.harvard.edu

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