Apicomplexan F-actin is required for efficient nuclear entry during host cell invasion

Del Rosario, M. et al. (2019) Apicomplexan F-actin is required for efficient nuclear entry during host cell invasion. EMBO Reports, 20(12), e48896. (doi: 10.15252/embr.201948896) (PMID:31584242) (PMCID:PMC6893294)

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The obligate intracellular parasites Toxoplasma gondii and Plasmodium spp. invade host cells by injecting a protein complex into the membrane of the targeted cell that bridges the two cells through the assembly of a ring‐like junction. This circular junction stretches while the parasites apply a traction force to pass through, a step that typically concurs with transient constriction of the parasite body. Here we analyse F‐actin dynamics during host cell invasion. Super‐resolution microscopy and real‐time imaging highlighted an F‐actin pool at the apex of pre‐invading parasite, an F‐actin ring at the junction area during invasion but also networks of perinuclear and posteriorly localised F‐actin. Mutant parasites with dysfunctional acto‐myosin showed significant decrease of junctional and perinuclear F‐actin and are coincidently affected in nuclear passage through the junction. We propose that the F‐actin machinery eases nuclear passage by stabilising the junction and pushing the nucleus through the constriction. Our analysis suggests that the junction opposes resistance to the passage of the parasite's nucleus and provides the first evidence for a dual contribution of actin‐forces during host cell invasion by apicomplexan parasites.

Item Type:Articles
Additional Information:This work was supported by an ERC‐Starting grant (ERC‐2012‐StG 309255‐EndoTox), a Wellcome 087582/Z/08/Z Senior Fellowship to MM, Wellcome 100993/Z/13/Z Investigator Award to JB and a National Secretariat for Higher Education, Sciences, Technology and Innovation of Ecuador (SENESCYT) PhD scholarship (IFTH‐GBE‐2015‐0475‐M) to MD. The Wellcome Centre for Molecular Parasitology is supported by core funding from the Wellcome (085349).
Glasgow Author(s) Enlighten ID:Pall, Dr Gurman and Del Rosario Minina, Mr Mario and Das, Dr Sujaan and Whitelaw, Mr Jamie and Periz, Dr Javier and Lemgruber Soares, Dr Leandro and Stortz, Mr Johannes
Authors: Del Rosario, M., Periz, J., Pavlou, G., Lyth, O., Latorre-Barragan, F., Das, S., Pall, G. S., Stortz, J., Lemgruber, L., Whitelaw, J., Baum, J., Tardieux, I., and Meisnner, M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:EMBO Reports
Publisher:EMBO Press
ISSN (Online):1469-3178
Published Online:04 October 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in EMBO Reports 20:e48896
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
162144Systematic analysis of essential parasite genes linked to invasion of the host cell in Toxoplasma gondiiMarkus MeissnerWellcome Trust (WELLCOTR)087582/Z/08/ZIII - Parasitology
166198Wellcome Trust 75th Anniversary Public Engagement ActivitiesAndrew WatersWellcome Trust (WELLCOTR)085349/Z/08/ZIII - Parasitology