Journal
ELIFE
Volume 8, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.49030
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Funding
- H2020 Excellent Science [ERC-2012-StG 309255-EndoTox]
- Wellcome Wellcome Senior Fellowship [103875/Z/14/Z]
- Horizon 2020 Framework Programme LMU Fellowship [H2020-MSCA-COFUND-2016-754388]
- Wellcome [085349]
- National Secretariat for Higher Education, Sciences, Technology and Innovation of Ecuador (SENESCYT) PhD scholarship [IFTH-GBE-2015-0475-M]
- Wellcome Trust [103875/Z/14/Z] Funding Source: Wellcome Trust
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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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