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Epistasis studies reveal redundancy among calcium-dependent protein kinases in motility and invasion of malaria parasites

Author

Listed:
  • Hanwei Fang

    (University of Geneva)

  • Ana Rita Gomes

    (Wellcome Trust Sanger Institute
    University of Montpellier)

  • Natacha Klages

    (University of Geneva)

  • Paco Pino

    (University of Geneva)

  • Bohumil Maco

    (University of Geneva)

  • Eloise M. Walker

    (London School of Hygiene &Tropical Medicine)

  • Zenon A. Zenonos

    (Wellcome Trust Sanger Institute
    MedImmune)

  • Fiona Angrisano

    (Imperial College London)

  • Jake Baum

    (Imperial College London)

  • Christian Doerig

    (Monash University)

  • David A. Baker

    (London School of Hygiene &Tropical Medicine)

  • Oliver Billker

    (Umeå University)

  • Mathieu Brochet

    (University of Geneva)

Abstract

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.

Suggested Citation

  • Hanwei Fang & Ana Rita Gomes & Natacha Klages & Paco Pino & Bohumil Maco & Eloise M. Walker & Zenon A. Zenonos & Fiona Angrisano & Jake Baum & Christian Doerig & David A. Baker & Oliver Billker & Math, 2018. "Epistasis studies reveal redundancy among calcium-dependent protein kinases in motility and invasion of malaria parasites," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06733-w
    DOI: 10.1038/s41467-018-06733-w
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    Cited by:

    1. Ravish Rashpa & Natacha Klages & Domitille Schvartz & Carla Pasquarello & Mathieu Brochet, 2023. "The Skp1-Cullin1-FBXO1 complex is a pleiotropic regulator required for the formation of gametes and motile forms in Plasmodium berghei," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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