{"doi":"10.1101/2025.11.21.689802","title":"A divergent <i>Plasmodium</i> NEK4 acts as a key regulator driving the early events of meiosis","abstract":"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 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":582892,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1494830,"name":"Molly Hair","orcid":"0009-0005-9352-9900","position":1,"is_corresponding":false},{"id":311423,"name":"Mohammad Zeeshan","orcid":"0000-0002-6185-403X","position":2,"is_corresponding":false},{"id":311425,"name":"David Ferguson","orcid":"0000-0001-5045-819X","position":3,"is_corresponding":false},{"id":311429,"name":"Declan Brady","orcid":"0000-0001-9150-7840","position":4,"is_corresponding":false},{"id":1495209,"name":"Carla Pasquarello","orcid":null,"position":5,"is_corresponding":false},{"id":311431,"name":"Andrew R. Bottrill","orcid":"0000-0002-5182-3643","position":6,"is_corresponding":false},{"id":1162093,"name":"Suhani Bhanvadia","orcid":null,"position":7,"is_corresponding":false},{"id":1313442,"name":"Arrmund Neal","orcid":"0000-0002-1735-4919","position":8,"is_corresponding":false},{"id":311426,"name":"Eelco C. Tromer","orcid":"0000-0003-3540-7727","position":9,"is_corresponding":false},{"id":32969,"name":"Karine G. Le Roch","orcid":"0000-0002-4862-9292","position":10,"is_corresponding":false},{"id":45706,"name":"Alexandre Hainard","orcid":"0009-0006-7403-3261","position":11,"is_corresponding":false},{"id":311432,"name":"Anthony A. Holder","orcid":"0000-0002-8490-6058","position":12,"is_corresponding":false},{"id":816942,"name":"Sue Vaughan","orcid":"0000-0002-0925-4491","position":13,"is_corresponding":false},{"id":311434,"name":"David S. Guttery","orcid":"0000-0003-0418-580X","position":14,"is_corresponding":false},{"id":311435,"name":"Rita Tewari","orcid":"0000-0003-3943-1847","position":15,"is_corresponding":false},{"id":1494829,"name":"Ryuji Yanase","orcid":"0000-0001-9419-398X","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:58:59.653747Z","pmid":"41332573","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}