An atypical Arp2/3 complex is required for Plasmodium DNA segregation and malaria transmission

IF 20.5 1区生物学 Q1 MICROBIOLOGY

Nature Microbiology Pub Date : 2025-06-13 DOI:10.1038/s41564-025-02023-6

Franziska Hentzschel, David Jewanski, Yvonne Sokolowski, Pratika Agarwal, Anna Kraeft, Kolja Hildenbrand, Lilian P. Dorner, Mirko Singer, Matthias Marti, Friedrich Frischknecht

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Abstract

Plasmodium parasites, the causative agents of malaria, undergo crucial developments within the mosquito vector, initiated by the formation of male and female gametes. Male gametogenesis involves three rapid rounds of mitosis without nuclear or cell division, followed by a single round of DNA segregation and nuclear division during gamete budding. How the cell organizes the segregation of eight genomes from a single octoploid nucleus into eight haploid gametes is currently unknown. Here we discovered an atypical Arp2/3 complex in Plasmodium important for DNA segregation during male gametogenesis. Unlike the canonical Arp2/3 complex found in other eukaryotes, Plasmodium Arp2/3 localizes to endomitotic spindles and interacts with a kinetochore-associated protein. Disruption of Arp2/3 subunits or actin polymerization interferes with kinetochore–spindle association, causes the formation of subhaploid gametes, and blocks transmission. Our work identified an evolutionary divergent Arp2/3 complex in malaria parasites, provides insights into gametogenesis, and reveals potential targets for transmission-blocking interventions.

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疟原虫DNA分离和疟疾传播需要非典型Arp2/3复合体

疟原虫是疟疾的病原体，在蚊子媒介中经历了关键的发展，由雄性和雌性配子的形成开始。雄性配子发生包括三轮快速的有丝分裂，没有核或细胞分裂，随后在配子出芽期间进行单轮DNA分离和核分裂。细胞如何将八个基因组从一个八倍体细胞核分离成八个单倍体配子目前尚不清楚。我们在疟原虫中发现了一个非典型的Arp2/3复合体，它在雄性配子体发生过程中对DNA分离很重要。与在其他真核生物中发现的典型Arp2/3复合物不同，疟原虫Arp2/3定位于内丝分裂纺锤体并与着丝点相关蛋白相互作用。Arp2/3亚基或肌动蛋白聚合的破坏干扰着丝点-纺锤体结合，导致亚单倍体配子的形成，并阻断传播。我们的工作确定了疟原虫中进化分化的Arp2/3复合体，为配子体发生提供了见解，并揭示了传播阻断干预的潜在靶点。

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来源期刊

Nature Microbiology Immunology and Microbiology-Microbiology

CiteScore

44.40

自引率

1.10%

发文量

226

期刊介绍： Nature Microbiology aims to cover a comprehensive range of topics related to microorganisms. This includes: Evolution: The journal is interested in exploring the evolutionary aspects of microorganisms. This may include research on their genetic diversity, adaptation, and speciation over time. Physiology and cell biology: Nature Microbiology seeks to understand the functions and characteristics of microorganisms at the cellular and physiological levels. This may involve studying their metabolism, growth patterns, and cellular processes. Interactions: The journal focuses on the interactions microorganisms have with each other, as well as their interactions with hosts or the environment. This encompasses investigations into microbial communities, symbiotic relationships, and microbial responses to different environments. Societal significance: Nature Microbiology recognizes the societal impact of microorganisms and welcomes studies that explore their practical applications. This may include research on microbial diseases, biotechnology, or environmental remediation. In summary, Nature Microbiology is interested in research related to the evolution, physiology and cell biology of microorganisms, their interactions, and their societal relevance.