Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum
- University of Glasgow, United Kingdom
- Ludwig-Maximillians University, Germany
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
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.
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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Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum
eLife 8:e49030.
https://doi.org/10.7554/eLife.49030
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