Epistasis studies reveal redundancy among calcium-dependent protein kinases in motility and invasion of malaria parasites
Autor: | Fang, Hanwei, Gomes, Ana Rita, Klages, Natacha, Pino, Paco, Maco, Bohumil, Walker, Eloise M., Zenonos, Zenon A., Angrisano, Fiona, Baum, Jake, Doerig, Christian, Baker, David A., Billker, Oliver, Brochet, Mathieu |
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Přispěvatelé: | Faculty of Medicine, University of Geneva, The Wellcome Trust Sanger Institute [Cambridge], Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), London School of Hygiene and Tropical Medicine (LSHTM), Department of Life Sciences, Imperial College London, Centre for Molecular Parasitology, University of Glasgow-Wellcome Trust, Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden, Université de Genève = University of Geneva (UNIGE), Umeå University, Wellcome Trust |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Male
HOST Plasmodium berghei Science [SDV]Life Sciences [q-bio] Plasmodium falciparum Protozoan Proteins Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology) Molecular Biology Microbiology Biochemistry or Biopharmacy) MOSQUITO TRANSMISSION Article SIGNALING PATHWAYS Mice MD Multidisciplinary parasitic diseases Cyclic GMP-Dependent Protein Kinases Animals [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology CELL Malaria Falciparum PHOSPHORYLATION lcsh:Science Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi) molekylärbiologi mikrobiologi biokemi eller biofarmaci) ddc:616 GLIDEOSOME Science & Technology PLASMODIUM-FALCIPARUM FUNCTIONAL-ANALYSIS GAMETOGENESIS Epistasis Genetic Multidisciplinary Sciences [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology TOXOPLASMA-GONDII Science & Technology - Other Topics Calcium Female lcsh:Q Protein Kinases |
Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018) Nature Communications Nature Communications, Nature Publishing Group, 2018, 9 (1), ⟨10.1038/s41467-018-06733-w⟩ Nature Communications, Vol. 9, No 1 (2018) P. 4248 Nature Communications, 2018, 9 (1), ⟨10.1038/s41467-018-06733-w⟩ |
ISSN: | 2041-1723 |
DOI: | 10.1038/s41467-018-06733-w |
Popis: | In malaria parasites, evolution of parasitism has been linked to functional optimisation. Despite this optimisation, most members of a calcium-dependent protein kinase (CDPK) family show genetic redundancy during erythrocytic proliferation. To identify relationships between phospho-signalling pathways, we here screen 294 genetic interactions among protein kinases in Plasmodium berghei. This reveals a synthetic negative interaction between a hypomorphic allele of the protein kinase G (PKG) and CDPK4 to control erythrocyte invasion which is conserved in P. falciparum. CDPK4 becomes critical when PKG-dependent calcium signals are attenuated to phosphorylate proteins important for the stability of the inner membrane complex, which serves as an anchor for the acto-myosin motor required for motility and invasion. Finally, we show that multiple kinases functionally complement CDPK4 during erythrocytic proliferation and transmission to the mosquito. This study reveals how CDPKs are wired within a stage-transcending signalling network to control motility and host cell invasion in malaria parasites. Despite functional optimisation during evolution of parasitism, most members of a calcium dependent protein kinase (CDPK) family show genetic redundancy in Plasmodium. Here, the authors screen 294 genetic interactions among protein kinases in Plasmodium and show how some CDPKs functionally interact to control motility and host cell invasion. |
Databáze: | OpenAIRE |
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