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

Ravish Rashpa (), Natacha Klages, Domitille Schvartz, Carla Pasquarello and Mathieu Brochet ()
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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

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36999-8

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