title: Plasmodium berghei MAPK1 displays differential and dynamic subcellular localizations during liver stage development.
abstract: Mitogen-activated protein kinases (MAPKs) regulate key signaling events in eukaryotic cells. In the genomes of protozoan Plasmodium parasites, the causative agents of malaria, two genes encoding kinases with significant homology to other eukaryotic MAPKs have been identified (mapk1, mapk2). In this work, we show that both genes are transcribed during Plasmodium berghei liver stage development, and analyze expression and subcellular localization of the PbMAPK1 protein in liver stage parasites. Live cell imaging of transgenic parasites expressing GFP-tagged PbMAPK1 revealed a nuclear localization of PbMAPK1 in the early schizont stage mediated by nuclear localization signals in the C-terminal domain. In contrast, a distinct localization of PbMAPK1 in comma/ring-shaped structures in proximity to the parasite's nuclei and the invaginating parasite membrane was observed during the cytomere stage of parasite development as well as in immature blood stage schizonts. The PbMAPK1 localization was found to be independent of integrity of a motif putatively involved in ATP binding, integrity of the putative activation motif and the presence of a predicted coiled-coil domain in the C-terminal domain. Although PbMAPK1 knock out parasites showed normal liver stage development, the kinase may still fulfill a dual function in both schizogony and merogony of liver stage parasites regulated by its dynamic and stage-dependent subcellular localization.
authors.affiliation: Department of Molecular Parasitology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Jannika Katharina
authors.initials: JK
authors.lastname: Wierk
authors.forename: Annette
authors.initials: A
authors.lastname: Langbehn
authors.forename: Maria
authors.initials: M
authors.lastname: Kamper
authors.forename: Stefanie
authors.initials: S
authors.lastname: Richter
authors.forename: Paul-Christian
authors.initials: PC
authors.lastname: Burda
authors.forename: Volker Theo
authors.initials: VT
authors.lastname: Heussler
authors.forename: Christina
authors.initials: C
authors.lastname: Deschermeier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055162:Biocatalysis; D002467:Cell Nucleus / Q000201:enzymology; D055786:Gene Knockout Techniques; D056945:Hep G2 Cells; D006801:Humans; D008018:Life Cycle Stages / Q000502:physiology*; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000469:parasitology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000378:metabolism; D010271:Parasites / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D010962:Plasmodium berghei / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D052939:Schizonts / Q000166:cytology / Q000201:enzymology; D013347:Subcellular Fractions / Q000201:enzymology
chemical_list: D019913:Nuclear Localization Signals; D019950:Mitogen-Activated Protein Kinase 1
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