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

## TL;DR

This paper identifies NEK4 as a crucial regulator linking meiosis and zygote development in the malaria parasite Plasmodium.

## Contribution

The study reveals NEK4's role in coordinating meiotic initiation with zygote morphogenesis in Plasmodium.

## Key findings

- NEK4 accumulates at the MTOC and APC, preceding microtubule assembly in Plasmodium zygotes.
- NEK4 deletion blocks MTOC duplication, microtubule formation, and nuclear migration.
- NEK4 absence disrupts transcriptional and phosphoregulatory networks essential for meiosis and cytoskeletal organization.

## Abstract

Meiosis is a conserved yet evolutionarily varied process underpinning sexual reproduction in eukaryotes. In the malaria parasite Plasmodium, meiosis is unconventional: it occurs immediately after fertilisation (post-zygotic) and must be coordinated with the transformation of the zygote into a motile ookinete. The mechanisms synchronising these meiotic and morphogenetic programmes remain unknow. Here, we identify the Plasmodium berghei NIMA-related kinase, NEK4 as a key regulator that couples meiotic initiation with zygote morphogenesis. Using ultrastructure expansion microscopy, we show that NEK4 accumulates at the microtubule-organising centre (MTOC) and the apical polar complex (APC) shortly after fertilisation, preceding the assembly of perinuclear and cortical microtubules. We reveal that Plasmodium zygotes undergo a nuclear migration driven by the MTOC, analogous to the meiotic nuclear movement in fission yeast. Deletion of nek4 results in complete developmental arrest: MTOC duplication and microtubule formation are blocked, chromatin remains uncondensed, and nuclear migration and cell polarity fail to establish. Transcriptomic and phosphoproteomic analyses reveal that NEK4 absence causes a collapse in transcriptional and phosphoregulatory networks governing meiosis and cytoskeletal organisation, leading to reduced expression and phosphorylation of important players, including HOP1, REC8, and AP2-O. These findings establish NEK4 as a key regulator driving meiotic entry and zygote maturation.