title: Regulation of Plasmodium falciparum development by calcium-dependent protein kinase 7 (PfCDPK7).
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.
authors.affiliation: From the Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi 110067, India.
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
authors.affiliation: From the Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi 110067, India.
authors.forename: Anuj
authors.initials: A
authors.lastname: Tripathi
authors.affiliation: From the Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi 110067, India.
authors.forename: Ravikant
authors.initials: R
authors.lastname: Ranjan
authors.affiliation: the Inserm-EPFL Joint Laboratory, Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Jean
authors.initials: J
authors.lastname: Halbert
authors.affiliation: the 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.
authors.forename: Tim
authors.initials: T
authors.lastname: Gilberger
authors.affiliation: the 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
authors.affiliation: From the Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi 110067, India, pushkar@nii.ac.in.
authors.forename: Pushkar
authors.initials: P
authors.lastname: Sharma
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D055786:Gene Knockout Techniques; D017125:Genes, Protozoan; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development*; D054730:Protein Interaction Domains and Motifs; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems; D017871:Calcium-Calmodulin-Dependent Protein Kinases
chemical_list: D019269:Phosphatidylinositol 4,5-Diphosphate; D011494:Protein Kinases; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases
keywords: Development; Kinase; Malaria; Phosphoinositide; Plasmodium; Protein Kinase; Signal