An Exported Kinase Family Mediates Species-Specific Erythrocyte Remodelling and Virulence in Human Malaria
Autor: | Hugo Belda, Moritz Treeck, Benoit Gamain, Viola Introini, Claudine Bisson, Malgorzata Broncel, Heledd Davies, Marta Tibúrcio, Dominique Dorin-Semblat, Jean-Philippe Semblat, Xingda Ye, Myrsini Kaforou |
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Přispěvatelé: | Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Microbiology (medical)
Proteomics Plasmodium Erythrocytes Immunology Protozoan Proteins Virulence Applied Microbiology and Biotechnology Microbiology Article 03 medical and health sciences Species Specificity parasitic diseases Protein Interaction Mapping Genetics Humans Protein Interaction Maps Phosphorylation 030304 developmental biology Host cell surface 0303 health sciences biology 030306 microbiology Kinase Phosphotransferases Phosphoproteomics Plasmodium falciparum Cell Biology biology.organism_classification Phosphoproteins 3. Good health Cell biology Malaria Bacterial adhesin [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Plasmodium knowlesi Gene Knockdown Techniques Multigene Family Gene Targeting Gene Deletion |
Zdroj: | Nature microbiology Nature Microbiology Nature Microbiology, Nature Publishing Group, 2020, 5 (6), pp.848-863. ⟨10.1038/s41564-020-0702-4⟩ |
ISSN: | 2058-5276 |
Popis: | Summary The most severe form of human malaria is caused by Plasmodium falciparum. Its virulence is closely linked to the increase in rigidity of infected erythrocytes and their adhesion to endothelial receptors, obstructing blood flow to vital organs. Unlike other human-infecting Plasmodium species, P. falciparum exports a family of 18 ‘FIKK’ serine/threonine kinases into the host cell, suggesting that phosphorylation may modulate erythrocyte modifications. We reveal substantial species-specific phosphorylation of erythrocyte proteins by P. falciparum, but not by Plasmodium knowlesi, which does not export FIKK kinases. By conditionally deleting all FIKK kinases combined with large-scale quantitative phosphoproteomics we identify unique phosphorylation fingerprints for each kinase, including phosphosites on parasite virulence factors and host erythrocyte proteins. Despite their non-overlapping target sites, a network analysis reveals that some FIKKs may act in the same pathways. Only deletion of the non-exported kinase FIKK8 resulted in reduced parasite growth, suggesting the exported FIKKs may instead support functions important for survival within the host. We show that one kinase, FIKK4.1, mediates both rigidification of the erythrocyte cytoskeleton and trafficking of the adhesin and key virulence factor PfEMP1 to the host cell surface. This establishes the FIKK family as important drivers of parasite evolution and malaria pathology. |
Databáze: | OpenAIRE |
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