1. Cell Biology
  2. Microbiology and Infectious Disease
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Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum

  1. Johannes Felix Stortz
  2. Mario Del Rosario
  3. Mirko Singer
  4. Jonathan M Wilkes
  5. Markus Meissner  Is a corresponding author
  6. Sujaan Das  Is a corresponding author
  1. University of Glasgow, United Kingdom
  2. Ludwig-Maximillians University, Germany
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Cite this article as: eLife 2019;8:e49030 doi: 10.7554/eLife.49030

Abstract

Plasmodium falciparum actin, apart from its role in erythrocyte invasion, is implicated in endocytosis, cytokinesis and inheritance of the chloroplast-like organelle - the apicoplast. However, the inability to visualise filamentous actin (F-actin) dynamics, a limitation we recently overcame for Toxoplasma (Periz et al, 2017), restricted characterisation of both F-actin and actin regulatory proteins. Here, we expressed and validated actin-binding chromobodies as F-actin-sensors in Plasmodium falciparum and characterised in-vivo actin dynamics. F-actin could be chemically modulated, and genetically disrupted upon conditionally deleting actin-1. In a comparative approach, we demonstrate that Formin-2, a predicted nucleator of F-actin, is responsible for apicoplast inheritance in both Plasmodium and Toxoplasma, and additionally mediates efficient cytokinesis in Plasmodium. Finally, time-averaged local intensity measurements of F-actin in Toxoplasma conditional mutants revealed molecular determinants of spatiotemporally regulated F-actin flow. Together, our data indicate that Formin-2 is the primary F-actin nucleator during apicomplexan intracellular growth, mediating multiple essential functions.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Proteomes of interest (Supplementary File 2) were downloaded from the UniProt-KB website (www.uniprot.org).

Article and author information

Author details

  1. Johannes Felix Stortz

    Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Mario Del Rosario

    Division of Infection and Immunity, Institute of Biomedical Life Sciences, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0430-1463
  3. Mirko Singer

    Faculty of Veterinary Medicine, Ludwig-Maximillians University, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Jonathan M Wilkes

    Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Markus Meissner

    Faculty of Veterinary Medicine, Ludwig-Maximillians University, Munich, Germany
    For correspondence
    Markus.Meissner@para.vetmed.uni-muenchen.de
    Competing interests
    The authors declare that no competing interests exist.
  6. Sujaan Das

    Faculty of Veterinary Medicine, Ludwig-Maximillians University, Munich, Germany
    For correspondence
    Sujaan.Das@para.vetmed.uni-muenchen.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6466-4258

Funding

H2020 Excellent Science (ERC-2012-StG 309255-EndoTox)

  • Markus Meissner

Wellcome (Wellcome Senior Fellowship 103875/Z/14/Z)

  • Markus Meissner

Horizon 2020 Framework Programme (LMU Fellowship H2020-MSCA-COFUND-2016-754388)

  • Sujaan Das

Wellcome (085349 - Core funding for the WCMP)

  • Johannes Felix Stortz
  • Mario Del Rosario
  • Jonathan M Wilkes
  • Markus Meissner
  • Sujaan Das

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Anna Akhmanova, Utrecht University, Netherlands

Publication history

  1. Received: June 5, 2019
  2. Accepted: July 17, 2019
  3. Accepted Manuscript published: July 19, 2019 (version 1)
  4. Version of Record published: August 9, 2019 (version 2)

Copyright

© 2019, Felix Stortz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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