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Cited by 8Malaria Research and ControlMicrotubule and mitosis dynamicsToxoplasma gondii Research Studies

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

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Hentzschel, Franziska, Jewanski, David, Sokolowski, Yvonne, Agarwal, Pratika, Kraeft, Anna, Hildenbrand, Kolja, Dorner, Lilian P., Singer, Mirko, Marti, Matthias, Frischknecht, Friedrich·2025·Nature Microbiology
DOI 10.1038/s41564-025-02023-6PMC PMC12222016

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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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Metadata

Authors
Hentzschel, F., Jewanski, D., Sokolowski, Y., Agarwal, P., Kraeft, A., Hildenbrand, K., Dorner, L. P., Singer, M., Marti, M., & Frischknecht, F.
Affiliations
  • Heidelberg University (DE)
  • University of Zurich (CH)
Corresponding author
  • Hentzschel, Franziska
  • Marti, Matthias
ORCID
Venue
Nature Microbiology
Publisher
Springer Science and Business Media LLC
Published
2025-06-13
Volume
10
Issue
7
Pages
1775-1790
ISSN
2058-5276 (ISSN-L)
DOI
10.1038/s41564-025-02023-6
PMC
PMC12222016
OpenAlex
W4411283018
Cited by
8
References
4
Citations by year
2026: 2 · 2025: 4
FWCI
5.46
Type
journal article
Language
en
Open access
Licence
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
  • Wellcome Trust (WT Investigator award 110166, Wellcome center award 104111)
  • Deutsches Zentrum für Infektionsforschung (TTU 03.813)
  • Deutsche Forschungsgemeinschaft (SPP 2225, SFB 1129, project number 240245660, SPP 2332)
  • Royal Society (Wolfson Merit award)
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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