A Modular Chromosomal Passenger Complex Rewires Chromosome Segregation in Plasmodium berghei

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The preprint studied how chromosome segregation is regulated in the malaria parasite Plasmodium berghei during male gametogenesis (mitosis) and subsequent zygote meiosis, focusing on the Aurora-related kinase ARK1 and its role in the chromosomal passenger complex (CPC). The authors report that ARK1 localizes to spindle poles, spindles, and kinetochores, and that ARK1 depletion produces short and multipolar spindles, kinetochore misalignment, and failed chromosome partitioning. They find that ARK1 forms a minimal CPC with INCENP1 during male gametogenesis, whereas meiosis involves a more elaborate CPC including INCENP2, kinetochores, centromeric histones, and spindle assembly checkpoint proteins, implying stage-specific modularity; a stated caveat is that the work is a preprint and not peer reviewed. Relevance to endometriosis: this paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Abstract Faithful chromosome segregation relies on precise kinetochore-microtubule interactions and checkpoint surveillance, yet the molecular basis of these processes varies widely across eukaryotes and is only beginning to be defined in apicomplexan parasites. In the malaria parasite Plasmodium berghei, chromosome segregation is especially critical during transmission from host to mosquito: rapid mitoses generate male gametes, and subsequent meiosis in the zygote seeds the next generation of infection. Here, we identify Aurora-related kinase 1 (ARK1) as a central regulator of chromosome segregation in both mitotic and meiotic contexts. ARK1 localises to spindle poles, spindles, and kinetochores, and its depletion results in short and multipolar spindles, kinetochore misalignment, and failed chromosome partitioning. ARK1 forms a minimal Chromosomal Passenger Complex (CPC) with INCENP1 during male gametogenesis, but a more elaborate CPC with INCENP2, kinetochores, centromeric histones, and spindle assembly checkpoint proteins during meiosis. This stage-specific modularity allows Plasmodium to prioritise male gamete formation whilst safeguarding faithful chromosome inheritance during zygote development, ensuring parasite transmission to the mosquito. Our findings demonstrate that conserved CPC principles are rewired in Plasmodium, highlighting both the plasticity of eukaryotic checkpoint control and a potential vulnerability for blocking malaria transmission.
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A Modular Chromosomal Passenger Complex Rewires Chromosome Segregation in Plasmodium berghei | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A Modular Chromosomal Passenger Complex Rewires Chromosome Segregation in Plasmodium berghei Lorenzo Brusini, Magali Roques, Chengyue Niu, Mathieu Brochet This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7545409/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Faithful chromosome segregation relies on precise kinetochore-microtubule interactions and checkpoint surveillance, yet the molecular basis of these processes varies widely across eukaryotes and is only beginning to be defined in apicomplexan parasites. In the malaria parasite Plasmodium berghei, chromosome segregation is especially critical during transmission from host to mosquito: rapid mitoses generate male gametes, and subsequent meiosis in the zygote seeds the next generation of infection. Here, we identify Aurora-related kinase 1 (ARK1) as a central regulator of chromosome segregation in both mitotic and meiotic contexts. ARK1 localises to spindle poles, spindles, and kinetochores, and its depletion results in short and multipolar spindles, kinetochore misalignment, and failed chromosome partitioning. ARK1 forms a minimal Chromosomal Passenger Complex (CPC) with INCENP1 during male gametogenesis, but a more elaborate CPC with INCENP2, kinetochores, centromeric histones, and spindle assembly checkpoint proteins during meiosis. This stage-specific modularity allows Plasmodium to prioritise male gamete formation whilst safeguarding faithful chromosome inheritance during zygote development, ensuring parasite transmission to the mosquito. Our findings demonstrate that conserved CPC principles are rewired in Plasmodium, highlighting both the plasticity of eukaryotic checkpoint control and a potential vulnerability for blocking malaria transmission. Biological sciences/Microbiology/Parasitology/Parasite biology Biological sciences/Microbiology/Parasitology/Parasite evolution Biological sciences/Cell biology/Cell division/Chromosome segregation Biological sciences/Cell biology/Cell division/Checkpoints Aurora kinase chromosomal passenger complex kinetochore Apicomplexa Plasmodium malaria evolutionary cell biology Full Text Additional Declarations There is NO Competing Interest. Supplementary Files TableS2.xls Table. S2 TableS1.xls Table. S1 TableS5.xls Table. S5 TableS4.xls Table. S4 TableS3.xls Table. S3 TableS6.xls Table. S6 TableS7.xls Table. S7 VideoS2.mp4 Video. S2 VideoS5.mp4 Video. S5 VideoS4.mp4 Video. S4 TableS8.xls Table. S8 VideoS3.mp4 Video. S3 VideoS6.mp4 Video. S6 VideoS7.mp4 Video. S7 VideoS1.mp4 Video. S1 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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