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<p>Meiosis is a conserved yet evolutionarily varied process underpinning sexual reproduction in eukaryotes. In the malaria parasite <i>Plasmodium</i>, 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 unknown. Here, we identify the <i>Plasmodium berghei</i> 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 <i>Plasmodium</i> zygotes undergo MTOC-associated nuclear migration, analogous to the meiotic nuclear movement in fission yeast. Deletion of the <i>Pbnek4</i> gene 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 absence of NEK4 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月12日

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  • Ryuji Yanase,
  • Molly Hair,
  • Mohammad Zeeshan,
  • David J. P. Ferguson,
  • Declan Brady,
  • Carla Pasquarello,
  • Andrew Bottrill,
  • Suhani Bhanvadia,
  • Armund Neal,
  • Eelco C. Tromer,
  • Karine G. Le Roch,
  • Alexandre Hainard,
  • Anthony A. Holder,
  • Sue Vaughan,
  • David S. Guttery,
  • Rita Tewari

摘要

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 unknown. 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 MTOC-associated nuclear migration, analogous to the meiotic nuclear movement in fission yeast. Deletion of the Pbnek4 gene 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 absence of NEK4 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.