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A non-canonical Arp2/3 complex is essential for Plasmodium DNA segregation and transmission of malaria.
Open accessPreprint — published as 10.1038/s41564-025-02023-6 · Paper page
Abstract
Plasmodium parasites, the causative agents of malaria, undergo a crucial development within the mosquito vector, initiated by the formation of male and female gametes from gametocytes. Male gametogenesis involves three rapid rounds of endomitosis followed by a single round of DNA segregation and nuclear division during gamete budding. How the cell organises the segregation of eight genomes from a single octoploid nucleus is currently unknown. Here, we discovered an atypical five-subunit Arp2/3 complex in Plasmodium essential for DNA segregation during male gametogenesis. Unlike the canonical seven-subunit Arp2/3 complex found in other eukaryotes, Plasmodium Arp2/3 localizes to endomitotic spindles and interacts with the kinetochores. Disruption of key Arp2/3 subunits or actin polymerization impedes proper DNA segregation, resulting in the formation of sub-haploid gametes and halting transmission. Our work identified an evolutionary divergent Arp2/3 protein complex in malaria parasites that offers novel insights into its function and potential targets for transmission-blocking interventions.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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Metadata
- Authors
- Hentzschel, F., Jewanski, D., Sokolowski, Y., Agarwal, P., Kraeft, A., Hildenbrand, K., Dorner, L., Singer, M., Marti, M., & Frischknecht, F.
- Affiliations
- Heidelberg University (DE)
- University of Zurich (CH)
- Corresponding author
- Hentzschel, Franziska
- Marti, Matthias
- ORCID
- Venue
- Nature Microbiology
- Published
- 2024-05-30
- Volume
- 10
- Issue
- 7
- Pages
- 1775-1790
- ISSN
- 2058-5276 (ISSN-L)
- PMC
- PMC12222016
- OpenAlex
- W4411283018
- Cited by
- 8
- References
- 1
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Microbiology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Deutsches Zentrum für Infektionsforschung (TTU 03.813)
- Wellcome Trust (110166)
- Royal Society
- University of Glasgow (104111)
- Deutsche Forschungsgemeinschaft (SPP2332, 240245660, SFB1129, SPP2225)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
- Keywords
- Arp2/3 complex, Plasmodium, male gametogenesis, DNA segregation, malaria transmission, endomitosis, actin polymerization, mosquito vectors, transmission-blocking interventions
- MeSH terms
- Actins, Animals, Female, Gametogenesis, Humans, Malaria, Male, Plasmodium, Plasmodium berghei, Protozoan Proteins, DNA, Protozoan, Kinetochores, Chromosome Segregation, Actin-Related Protein 2-3 Complex
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