A divergent Plasmodium NEK4 acts as a key regulator driving the early events of meiosis

ABSTRACT: Meiosis is a conserved yet evolutionarily varied process that underpins sexual reproduction in eukaryotes. In the malaria parasite Plasmodium, meiosis occurs within the mosquito midgut immediately after fertilisation, as the diploid zygote differentiates into a motile ookinete. Here, we identify the Plasmodium berghei NIMA-related kinase, NEK4 as a key regulator that coordinates meiotic initiation with zygote morphogenesis. The process is highly divergent from that of most canonical models, since many conserved meiotic regulators are absent, and employs lineage-specific adaptations of protein function. Using gene tagging and ultrastructure expansion microscopy, we show that NEK4 is located at the microtubule-organising centre (MTOC) and the apical polar complex (APC) during early zygote development. NEK4-GFP foci appear shortly after fertilisation, followed by perinuclear and cortical microtubule formation. Deletion of nek4 results in complete developmental arrest: MTOC duplication and DNA replication are blocked, chromatin remains uncondensed, and nuclear migration and cell polarity fail to establish. Transcriptomic and phosphoproteomic analyses revealed that absence of NEK4 causes a collapse in transcriptional and phosphoregulatory networks controlling meiosis and cytoskeletal organisation. nek4 gene knockout parasites had reduced expression of genes linked to meiotic division, motility, and differentiation, and reduced phosphorylation of important players such as DMC1, AP2-Z, Pb103, HOP1, and REC8 proteins. These findings establish NEK4 as a key molecule governing transcriptional activation, protein synthesis, and phosphoregulation to drive meiotic entry and zygote maturation.

INSTRUMENT(S):

ORGANISM(S): Plasmodium Berghei Anka

SUBMITTER: Andrew Bottrill  

LAB HEAD: Professor Rita Tewari

PROVIDER: PXD070161 | Pride | 2026-04-16

REPOSITORIES: Pride