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Concerted Action of Two Formins in Gliding Motility and Host Cell Invasion by Toxoplasma gondii

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2010
Author Daher Wassim, Plattner Fabienne, Carlier Marie France, Soldati-Favre Dominique,
Project Study of factors governing the invasive and replicative modes in Apicomplexa
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Original article (peer-reviewed)

Journal PloS Pathogens
Volume (Issue) 6
Page(s) e1001132 - e1001146
Title of proceedings PloS Pathogens
DOI 20949068

Open Access

URL http://www.ncbi.nlm.nih.gov/pubmed/20949068
Type of Open Access Publisher (Gold Open Access)

Abstract

The invasive forms of apicomplexan parasites share a conserved form of gliding motility that powers parasite migration across biological barriers, host cell invasion and egress from infected cells. Previous studies have established that the duration and direction of gliding motility are determined by actin polymerization; however, regulators of actin dynamics in apicomplexans remain poorly characterized. In the absence of a complete ARP2/3 complex, the formin homology 2 domain containing proteins and the accessory protein profilin are presumed to orchestrate actin polymerization during host cell invasion. Here, we have undertaken the biochemical and functional characterization of two Toxoplasma gondii formins and established that they act in concert as actin nucleators during invasion. The importance of TgFRM1 for parasite motility has been assessed by conditional gene disruption. The contribution of each formin individually and jointly was revealed by an approach based upon the expression of dominant mutants with modified FH2 domains impaired in actin binding but still able to dimerize with their respective endogenous formin. These mutated FH2 domains were fused to the ligand-controlled destabilization domain (DD-FKBP) to achieve conditional expression. This strategy proved unique in identifying the nonredundant and critical roles of both formins in invasion. These findings provide new insights into how controlled actin polymerization drives the directional movement required for productive penetration of parasites into host cells.
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