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

In addition to its role in erythrocyte invasion, Plasmodium falciparum actin is implicated in endocytosis, cytokinesis and inheritance of the chloroplast-like organelle called the apicoplast. Previously, the inability to visualise filamentous actin (F-actin) dynamics had restricted the characterisat...

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Autores principales: Stortz, Johannes Felix, Del Rosario, Mario, Singer, Mirko, Wilkes, Jonathan M, Meissner, Markus, Das, Sujaan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688858/
https://www.ncbi.nlm.nih.gov/pubmed/31322501
http://dx.doi.org/10.7554/eLife.49030
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author Stortz, Johannes Felix
Del Rosario, Mario
Singer, Mirko
Wilkes, Jonathan M
Meissner, Markus
Das, Sujaan
author_facet Stortz, Johannes Felix
Del Rosario, Mario
Singer, Mirko
Wilkes, Jonathan M
Meissner, Markus
Das, Sujaan
author_sort Stortz, Johannes Felix
collection PubMed
description In addition to its role in erythrocyte invasion, Plasmodium falciparum actin is implicated in endocytosis, cytokinesis and inheritance of the chloroplast-like organelle called the apicoplast. Previously, the inability to visualise filamentous actin (F-actin) dynamics had restricted the characterisation of both F-actin and actin regulatory proteins, a limitation we recently overcame for Toxoplasma (Periz et al, 2017). Here, we have 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.
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spelling pubmed-66888582019-08-12 Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum Stortz, Johannes Felix Del Rosario, Mario Singer, Mirko Wilkes, Jonathan M Meissner, Markus Das, Sujaan eLife Cell Biology In addition to its role in erythrocyte invasion, Plasmodium falciparum actin is implicated in endocytosis, cytokinesis and inheritance of the chloroplast-like organelle called the apicoplast. Previously, the inability to visualise filamentous actin (F-actin) dynamics had restricted the characterisation of both F-actin and actin regulatory proteins, a limitation we recently overcame for Toxoplasma (Periz et al, 2017). Here, we have 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. eLife Sciences Publications, Ltd 2019-07-19 /pmc/articles/PMC6688858/ /pubmed/31322501 http://dx.doi.org/10.7554/eLife.49030 Text en © 2019, Stortz et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Stortz, Johannes Felix
Del Rosario, Mario
Singer, Mirko
Wilkes, Jonathan M
Meissner, Markus
Das, Sujaan
Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum
title Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum
title_full Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum
title_fullStr Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum
title_full_unstemmed Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum
title_short Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum
title_sort formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in plasmodium falciparum
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688858/
https://www.ncbi.nlm.nih.gov/pubmed/31322501
http://dx.doi.org/10.7554/eLife.49030
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