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

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A non-canonical Arp2/3 complex is essential for Plasmodium DNA segregation and transmission of malaria

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Hentzschel, Franziska, Jewanski, David, Sokolowski, Yvonne, Agarwal, Pratika, Kraeft, Anna, Hildenbrand, Kolja, Dorner, Lilian P., Singer, Mirko, Frischknecht, Friedrich, Marti, Matthias·2023·Nature Microbiology
DOI 10.1101/2023.10.25.563799PMC PMC12222016

Preprint — published as 10.1038/s41564-025-02023-6 · Paper page

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Abstract

The malaria-causing parasite Plasmodium has a complex life cycle involving both vertebrate and mosquito hosts. Sexual stages or gametocytes are the only stage competent for transmission to mosquitoes. Formation of flagellated male gametes from gametocytes requires rapid rounds of genome replication. Here we discovered a non-canonical Plasmodium actin-related protein 2/3 (Arp2/3) complex essential for DNA segregation during male gametogenesis. Plasmodium Arp2/3 dynamically localizes within the nucleus to the endomitotic spindles and interacts with a kinetochore protein. Deletion of key Arp2/3 subunits or interfering with actin polymerisation leads to the formation of sub-haploid male gametes and a complete block in transmission through delayed developmental arrest at the oocyst stage. Our work identified an evolutionary divergent protein complex in malaria parasites that offers 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., Frischknecht, F., & Marti, M.
Affiliations
  • Heidelberg University (DE)
  • University of Zurich (CH)
Corresponding author
  • Hentzschel, Franziska
  • Marti, Matthias
ORCID
Venue
Nature Microbiology
Publisher
openRxiv
Published
2023-10-26
Volume
10
Issue
7
Pages
1775-1790
ISSN
2058-5276 (ISSN-L)
DOI
10.1101/2023.10.25.563799
PMC
PMC12222016
OpenAlex
W4411283018
Cited by
8
References
1
Citations by year
2026: 2 · 2025: 4 · 2024: 2
FWCI
5.37
Type
journal article
Language
en
Open access
Licence
cc-by
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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