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

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 complex showing tightly regulated expression and localisation across multiple developmental stages. It regulates cell division by controlling nucleus segregation during schizogony and centrosome partitioning during microgametogenesis. It additionally controls parasite-specific processes including gamete egress from the host erythrocyte, as well as formation of the merozoite apical complex and the ookinete inner membrane complex (IMC), two structures essential for Plasmodium dissemination, moreover it is critical for zygote to ookinete conversation. Ubiquitinomic surveys reveal a large set of proteins ubiquitinated in an FBXO1-dependent manner including proteins important for egress and IMC organisation. We additionally demonstrate bidirectional interplay between ubiquitination and phosphorylation via calcium-dependent protein kinase 1. Altogether we show that Plasmodium SCFFBXO1 plays conserved roles in cell division and additionally controls parasite-specific processes in the mammalian and mosquito hosts.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Plasmodium Berghei Anka

DISEASE(S): Malaria

SUBMITTER: alexandre Hainard  

LAB HEAD: Mathieu Brochet

PROVIDER: PXD035557 | Pride | 2023-02-17

REPOSITORIES: Pride