Dataset Information

Plasmodium berghei zygotes of WT and Pbnek4-ko lines at 0 and 2 hpa phosphoproteomics

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. Meiosis in Plasmodium spp. 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 regulator governing transcriptional activation, protein synthesis, and phosphoregulation to drive meiotic entry and zygote maturation.

INSTRUMENT(S):

ORGANISM(S): Plasmodium Berghei Anka

TISSUE(S): Zygote

DISEASE(S): Malaria

SUBMITTER: Ryuji Yanase

LAB HEAD: Rita Tewari

PROVIDER: PXD070965 | Pride | 2026-04-16

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20241121_LU50HMC08_pl24071_RY_phospho.raw	Raw
	20241121_LU50HMC10_pl24071_RY_FT.raw	Raw
	checksum.txt	Txt
	pl24071_RYanase_FT.mzML	Mzml
	pl24071_RYanase_FT.mzid	Mzid

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Publications

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

Yanase Ryuji R Hair Molly M Zeeshan Mohammad M Ferguson David J P DJP Brady Declan D Pasquarello Carla C Bottrill Andrew A Bhanvadia Suhani S Neal Arrmund A Tromer Eelco C EC Le Roch Karine G KG Hainard Alexandre A Holder Anthony A AA Vaughan Sue S Guttery David S DS Tewari Rita R

Research square 20251209

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 th ...[more]

PMID: 41510253

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Project description:Ray2013 - Meiotic initiation in S. cerevisiae A mathematical representation of early meiotic events, particularly feedback mechanisms at the system level and phosphorylation of signalling molecules for regulating protein activities, is described here This model is described in the article: Dynamic modeling of yeast meiotic initiation. Ray D, Su Y, Ye P. BMC Syst Biol. 2013 May 1;7:37 Abstract: BACKGROUND: Meiosis is the sexual reproduction process common to eukaryotes. The diploid yeast Saccharomyces cerevisiae undergoes meiosis in sporulation medium to form four haploid spores. Initiation of the process is tightly controlled by intricate networks of positive and negative feedback loops. Intriguingly, expression of early meiotic proteins occurs within a narrow time window. Further, sporulation efficiency is strikingly different for yeast strains with distinct mutations or genetic backgrounds. To investigate signal transduction pathways that regulate transient protein expression and sporulation efficiency, we develop a mathematical model using ordinary differential equations. The model describes early meiotic events, particularly feedback mechanisms at the system level and phosphorylation of signaling molecules for regulating protein activities. RESULTS: The mathematical model is capable of simulating the orderly and transient dynamics of meiotic proteins including Ime1, the master regulator of meiotic initiation, and Ime2, a kinase encoded by an early gene. The model is validated by quantitative sporulation phenotypes of single-gene knockouts. Thus, we can use the model to make novel predictions on the cooperation between proteins in the signaling pathway. Virtual perturbations on feedback loops suggest that both positive and negative feedback loops are required to terminate expression of early meiotic proteins. Bifurcation analyses on feedback loops indicate that multiple feedback loops are coordinated to modulate sporulation efficiency. In particular, positive auto-regulation of Ime2 produces a bistable system with a normal meiotic state and a more efficient meiotic state. CONCLUSIONS: By systematically scanning through feedback loops in the mathematical model, we demonstrate that, in yeast, the decisions to terminate protein expression and to sporulate at different efficiencies stem from feedback signals toward the master regulator Ime1 and the early meiotic protein Ime2. We argue that the architecture of meiotic initiation pathway generates a robust mechanism that assures a rapid and complete transition into meiosis. This type of systems-level regulation is a commonly used mechanism controlling developmental programs in yeast and other organisms. Our mathematical model uncovers key regulations that can be manipulated to enhance sporulation efficiency, an important first step in the development of new strategies for producing gametes with high quality and quantity. This model is hosted on BioModels Database and identified by: BIOMD0000000626 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Plasmodium berghei zygotes of WT and Pbnek4-ko lines at 0 and 2 hpa phosphoproteomics

Dataset's files

Publications

A divergent <i>Plasmodium</i> NEK4 acts as a key regulator driving the early events of meiosis.

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Dataset Information

Plasmodium berghei zygotes of WT and Pbnek4-ko lines at 0 and 2 hpa phosphoproteomics

Dataset's files

Publications

A divergent &lt;i&gt;Plasmodium&lt;/i&gt; NEK4 acts as a key regulator driving the early events of meiosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

A divergent <i>Plasmodium</i> NEK4 acts as a key regulator driving the early events of meiosis.