Hentzschel Franziska, Jewanski David, Sokolowski Yvonne, Agarwal Pratika, Kraeft Anna, Hildenbrand Kolja, Dorner Lilian P, Singer Mirko, Marti Matthias, Frischknecht Friedrich
Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, UK.
Integrative Parasitology, Centre for Infectious Diseases, Heidelberg University Medical Faculty, Heidelberg, Germany.
Nat Microbiol. 2025 Jun 13. doi: 10.1038/s41564-025-02023-6.
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.
疟原虫是疟疾的病原体，在蚊媒体内经历关键发育过程，这一过程由雄配子和雌配子的形成引发。雄配子发生包括三轮快速的有丝分裂，期间无核分裂或细胞分裂，随后在配子出芽过程中进行一轮DNA分离和核分裂。目前尚不清楚细胞如何将单个八倍体细胞核中的八个基因组分离到八个单倍体配子中。在此，我们在疟原虫中发现了一种非典型的Arp2/3复合物，它对雄配子发生过程中的DNA分离至关重要。与其他真核生物中发现的经典Arp2/3复合物不同，疟原虫Arp2/3定位于核内有丝分裂纺锤体，并与一种动粒相关蛋白相互作用。Arp2/3亚基的破坏或肌动蛋白聚合会干扰动粒-纺锤体的结合，导致亚单倍体配子的形成，并阻断传播。我们的研究确定了疟原虫中一种进化上不同的Arp2/3复合物，为配子发生提供了见解，并揭示了传播阻断干预的潜在靶点。
