Molecular Characterization of Toxoplasma gondii Formin 3, an Actin Nucleator Dispensable for Tachyzoite Growth and Motility

Daher, Wassim; Klages Jemelin, Natacha; Carlier, Marie-France; Soldati-Favre, Dominique

doi:10.1128/EC.05192-11

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Title		Molecular Characterization of Toxoplasma gondii Formin 3, an Actin Nucleator Dispensable for Tachyzoite Growth and Motility
Authors		Daher, Wassim Klages Jemelin, Natacha Carlier, Marie-France Soldati-Favre, Dominique
Published in		Eukaryotic Cell. 2012, vol. 11, no. 3, p. 343-52
Abstract		Toxoplasma gondii belongs to the phylum Apicomplexa, a group of obligate intracellular parasites that rely on gliding motility to enter host cells. Drugs interfering with the actin cytoskeleton block parasite motility, host cell invasion, and egress from infected cells. Myosin A, profilin, formin 1, formin 2, and actin-depolymerizing factor have all been implicated in parasite motility, yet little is known regarding the importance of actin polymerization and other myosins for the remaining steps of the parasite lytic cycle. Here we establish that T. gondii formin 3 (TgFRM3), a newly described formin homology 2 domain (FH2)-containing protein, binds to Toxoplasma actin and nucleates rabbit actin assembly in vitro. TgFRM3 expressed as a transgene exhibits a patchy localization at several distinct structures within the parasite. Disruption of the TgFRM3 gene by double homologous recombination in a ku80-ko strain reveals no vital function for tachyzoite propagation in vitro, which is consistent with its weak level of expression in this life stage. Conditional stabilization of truncated forms of TgFRM3 suggests that different regions of the molecule contribute to distinct localizations. Moreover, expression of TgFRM3 lacking the C-terminal domain severely affects parasite growth and replication. This work provides a first insight into how this specialized formin, restricted to the group of coccidia, completes its actin-nucleating activity.
Identifiers		DOI: 10.1128/EC.05192-11 PMID: 22210829
Full text		Article (Accepted version) (1.7 MB) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire
Research group		Biologie d'un parasite intracellulaire obligatoire (773)
Citation (ISO format)		DAHER, Wassim et al. Molecular Characterization of Toxoplasma gondii Formin 3, an Actin Nucleator Dispensable for Tachyzoite Growth and Motility. In: Eukaryotic Cell, 2012, vol. 11, n° 3, p. 343-52. doi: 10.1128/EC.05192-11 https://archive-ouverte.unige.ch/unige:18953