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Multiple essential functions of Plasmodium falciparum actin-1 during malaria blood-stage development

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Title: Multiple essential functions of Plasmodium falciparum actin-1 during malaria blood-stage development
Authors: Das, S
Lemgruber, L
Tay, CL
Baum, J
Meissner, M
Item Type: Journal Article
Abstract: Background: The phylum Apicomplexa includes intracellular parasites causing immense global disease burden, the deadliest of them being the human malaria parasite Plasmodium falciparum, which invades and replicates within erythrocytes. The cytoskeletal protein actin is well conserved within apicomplexans but divergent from mammalian actins, and was primarily reported to function during host cell invasion. However, novel invasion mechanisms have been described for several apicomplexans, and specific functions of the acto-myosin system are being reinvestigated. Of the two actin genes in P. falciparum, actin-1 (pfact1) is ubiquitously expressed in all life-cycle stages and is thought to be required for erythrocyte invasion, although its functions during parasite development are unknown, and definitive in vivo characterisation during invasion is lacking. Results: Here we have used a conditional Cre-lox system to investigate the functions of PfACT1 during P. falciparum bloodstage development and host cell invasion. We demonstrate that PfACT1 is crucially required for segregation of the plastid-like organelle, the apicoplast, and for efficient daughter cell separation during the final stages of cytokinesis. Surprisingly, we observe that egress from the host cell is not an actin-dependent process. Finally, we show that parasites lacking PfACT1 are capable of microneme secretion, attachment and formation of a junction with the erythrocyte, but are incapable of host cell invasion. Conclusions: This study provides important mechanistic insights into the definitive essential functions of PfACT1 in P. falciparum, which are not only of biological interest, but owing to functional divergence from mammalian actins, could also form the basis for the development of novel therapeutics against apicomplexans.
Issue Date: 15-Aug-2017
Date of Acceptance: 14-Jul-2017
URI: http://hdl.handle.net/10044/1/50127
DOI: https://dx.doi.org/10.1186/s12915-017-0406-2
ISSN: 1741-7007
Publisher: BioMed Central
Journal / Book Title: BMC Biology
Volume: 15
Copyright Statement: © Meissner et al. 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 100993/Z/13/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
Actin
Cytoskeleton
Invasion
Apicoplast
Cytokinesis
Egress
Merozoite
Apicomplexa
Malaria
Plasmodium
Plasmodium falciparum
Actomyosin
Conditional gene disruption
HOST-CELL INVASION
TOXOPLASMA-GONDII
APICOMPLEXAN PARASITES
HUMAN ERYTHROCYTE
PROTEIN
MYOSIN
INSIGHTS
DYNAMICS
MOTILITY
EGRESS
06 Biological Sciences
Developmental Biology
Publication Status: Published
Article Number: 70
Appears in Collections:Faculty of Natural Sciences



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