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The Skp1-Cullin1-FBXO1 complex is a pleiotropic regulator required for the formation of gametes and motile forms in Plasmodium berghei

Author

Listed:
  • Ravish Rashpa

    (University of Geneva, Faculty of Medicine, Department of Microbiology and Molecular Medicine)

  • Natacha Klages

    (University of Geneva, Faculty of Medicine, Department of Microbiology and Molecular Medicine)

  • Domitille Schvartz

    (University of Geneva, Faculty of Medicine, Proteomics Core Facility)

  • Carla Pasquarello

    (University of Geneva, Faculty of Medicine, Proteomics Core Facility)

  • Mathieu Brochet

    (University of Geneva, Faculty of Medicine, Department of Microbiology and Molecular Medicine)

Abstract

Malaria-causing parasites of the Plasmodium genus undergo multiple developmental phases in the human and the mosquito hosts, regulated by various post-translational modifications. While ubiquitination by multi-component E3 ligases is key to regulate a wide range of cellular processes in eukaryotes, little is known about its role in Plasmodium. Here we show that Plasmodium berghei expresses a conserved SKP1/Cullin1/FBXO1 (SCFFBXO1) complex showing tightly regulated expression and localisation across multiple developmental stages. It is key to cell division for nuclear segregation during schizogony and centrosome partitioning during microgametogenesis. It is additionally required for parasite-specific processes including gamete egress from the host erythrocyte, as well as integrity of the apical and the inner membrane complexes (IMC) in merozoite and ookinete, two structures essential for the dissemination of these motile stages. Ubiquitinomic surveys reveal a large set of proteins ubiquitinated in a FBXO1-dependent manner including proteins important for egress and IMC organisation. We additionally demonstrate an interplay between FBXO1-dependent ubiquitination and phosphorylation via calcium-dependent protein kinase 1. Altogether we show that Plasmodium SCFFBXO1 plays conserved roles in cell division and is also important for parasite-specific processes in the mammalian and mosquito hosts.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36999-8
    DOI: 10.1038/s41467-023-36999-8
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    References listed on IDEAS

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    1. 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.
    2. O. Billker & V. Lindo & M. Panico & A. E. Etienne & T. Paxton & A. Dell & M. Rogers & R. E. Sinden & H. R. Morris, 1998. "Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito," Nature, Nature, vol. 392(6673), pages 289-292, March.
    3. Sudhir Kumar & Manish Kumar & Roseleen Ekka & Jeffrey D. Dvorin & Aditya S. Paul & Anil K. Madugundu & Tim Gilberger & Harsha Gowda & Manoj T. Duraisingh & T. S. Keshava Prasad & Pushkar Sharma, 2017. "PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    4. Ons M’Saad & Joerg Bewersdorf, 2020. "Light microscopy of proteins in their ultrastructural context," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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