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.
Metrics
-
- 3,222
- views
-
- 405
- downloads
-
- 39
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
Further reading
-
- Microbiology and Infectious Disease
eLife has recently published a wide range of papers on malaria, covering a diversity of themes including parasite biology, epidemiology, immunology, drugs and vaccines.
-
- Cell Biology
- Neuroscience
The emergence of Aβ pathology is one of the hallmarks of Alzheimer’s disease (AD), but the mechanisms and impact of Aβ in progression of the disease is unclear. The nuclear pore complex (NPC) is a multi-protein assembly in mammalian cells that regulates movement of macromolecules across the nuclear envelope; its function is shown to undergo age-dependent decline during normal aging and is also impaired in multiple neurodegenerative disorders. Yet not much is known about the impact of Aβ on NPC function in neurons. Here, we examined NPC and nucleoporin (NUP) distribution and nucleocytoplasmic transport using a mouse model of AD (AppNL-G-F/NL-G-F) that expresses Aβ in young animals. Our studies revealed that a time-dependent accumulation of intracellular Aβ corresponded with a reduction of NPCs and NUPs in the nuclear envelope which resulted in the degradation of the permeability barrier and inefficient segregation of nucleocytoplasmic proteins, and active transport. As a result of the NPC dysfunction App KI neurons become more vulnerable to inflammation-induced necroptosis – a programmed cell death pathway where the core components are activated via phosphorylation through nucleocytoplasmic shutting. Collectively, our data implicates Aβ in progressive impairment of nuclear pore function and further confirms that the protein complex is vulnerable to disruption in various neurodegenerative diseases and is a potential therapeutic target.
