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 |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Del Rosario Minina, Mr Mario and Stortz, Johannes Felix and Wilkes, Dr Jonathan and Das, Dr Sujaan and Meissner, Professor Markus |
Creator Roles: | Meissner, M.Conceptualization, Project administration, Resources, Supervision, Writing – original draft, Writing – review and editing Das, S.Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review and editing Stortz, J. F.Formal analysis, Investigation, Methodology, Writing – original draft Del Rosario Minina, M.Formal analysis, Methodology, Validation Wilkes, J.Formal analysis, Investigation, Methodology |
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 > School of Infection & Immunity |
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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