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J Biol Chem. 2014 Jul 18;289(29):20386-95. doi: 10.1074/jbc.M114.561670. Epub 2014 Jun 3.

Regulation of Plasmodium falciparum development by calcium-dependent protein kinase 7 (PfCDPK7).

Author information

  • 1From the Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi 110067, India.
  • 2the Inserm-EPFL Joint Laboratory, Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
  • 3the Department of Pathology and Molecular Medicine, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4L8, Canada, the Bernhard-Nocht-Institute for Tropical Medicine, 20359 Hamburg, Germany, and.
  • 4the Inserm-EPFL Joint Laboratory, Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland, the Department of Microbiology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
  • 5From the Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi 110067, India, pushkar@nii.ac.in.

Abstract

Second messengers such as phosphoinositides and calcium are known to control diverse processes involved in the development of malaria parasites. However, the underlying molecular mechanisms and pathways need to be unraveled, which may be achieved by understanding the regulation of effectors of these second messengers. Calcium-dependent protein kinase (CDPK) family members regulate diverse parasitic processes. Because CDPKs are absent from the host, these kinases are considered as potential drug targets. We have dissected the function of an atypical CDPK from Plasmodium falciparum, PfCDPK7. The domain architecture of PfCDPK7 is very different from that of other CDPKs; it has a pleckstrin homology domain adjacent to the kinase domain and two calcium-binding EF-hands at its N terminus. We demonstrate that PfCDPK7 interacts with PI(4,5)P2 via its pleckstrin homology domain, which may guide its subcellular localization. Disruption of PfCDPK7 caused a marked reduction in the growth of the blood stage parasites, as maturation of rings to trophozoites was markedly stalled. In addition, parasite proliferation was significantly attenuated. These findings shed light on an important role for PfCDPK7 in the erythrocytic asexual cycle of malaria parasites.

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

KEYWORDS:

Development; Kinase; Malaria; Phosphoinositide; Plasmodium; Protein Kinase; Signal

PMID:
24895132
[PubMed - indexed for MEDLINE]
PMCID:
PMC4106351
Free PMC Article
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