title: Regulation of Plasmodium falciparum glideosome associated protein 45 (PfGAP45) phosphorylation.
abstract: The actomyosin motor complex of the glideosome provides the force needed by apicomplexan parasites such as Toxoplasma gondii (Tg) and Plasmodium falciparum (Pf) to invade their host cells and for gliding motility of their motile forms. Glideosome Associated Protein 45 (PfGAP45) is an essential component of the glideosome complex as it facilitates anchoring and effective functioning of the motor. Dissection of events that regulate PfGAP45 may provide insights into how the motor and the glideosome operate. We found that PfGAP45 is phosphorylated in response to Phospholipase C (PLC) and calcium signaling. It is phosphorylated by P. falciparum kinases Protein Kinase B (PfPKB) and Calcium Dependent Protein Kinase 1 (PfCDPK1), which are calcium dependent enzymes, at S89, S103 and S149. The Phospholipase C pathway influenced the phosphorylation of S103 and S149. The phosphorylation of PfGAP45 at these sites is differentially regulated during parasite development. The localization of PfGAP45 and its association may be independent of the phosphorylation of these sites. PfGAP45 regulation in response to calcium fits in well with the previously described role of calcium in host cell invasion by malaria parasite.
authors.affiliation: Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Divya Catherine
authors.initials: DC
authors.lastname: Thomas
authors.forename: Anwar
authors.initials: A
authors.lastname: Ahmed
authors.forename: Tim Wolf
authors.initials: TW
authors.lastname: Gilberger
authors.forename: Pushkar
authors.initials: P
authors.lastname: Sharma
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000254:growth & development; D011494:Protein Kinases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases
chemical_list: D002118:Calcium; D008565:Membrane Proteins; D011494:Protein Kinases; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D010738:Type C Phospholipases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C509918:glideosome-associated protein 45, Plasmodium falciparum; C487499:PKB protein, Plasmodium falciparum; C531238:calcium-dependent protein kinase-1, Plasmodium falciparum