Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum

Stortz, J. F., Del Rosario, M., Singer, M., Wilkes, J. M. , Meissner, M. and Das, S. (2019) Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum. eLife, 8, e49030. (doi:10.7554/eLife.49030) (PMID:31322501)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Meissner, Professor Markus and Del Rosario Minina, Mr Mario and Wilkes, Dr Jonathan and Das, Dr Sujaan and Stortz, Johannes Felix
Authors: Stortz, J. F., Del Rosario, M., Singer, M., Wilkes, J. M., Meissner, M., and Das, S.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2050-084X
ISSN (Online):2050-084X
Published Online:19 July 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in eLife 8: e49030
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
592941EndoTox: Endosomal dependent transport to the unique secretory organelles of apicomplexan parasitesMarkus MeissnerEuropean Research Council (ERC)309255III - PARASITOLOGY
653211Essential or redundant: Dissection of apicomplexan invasion mechanismsMarkus MeissnerWellcome Trust (WELLCOTR)103875/Z/14/ZIII - PARASITOLOGY
371798The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)085349/B/08/ZIII - PARASITOLOGY