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BMC Biology

, 12:773

First Online: 31 December 2014Received: 27 September 2014Accepted: 10 December 2014DOI: 10.1186-s12915-014-0108-y

Cite this article as: Bichet, M., Joly, C., Hadj Henni, A. et al. BMC Biol 2014 12: 773. doi:10.1186-s12915-014-0108-y

Abstract

BackgroundThe public health threats imposed by toxoplasmosis worldwide and by malaria in sub-Saharan countries are directly associated with the capacity of their related causative agents Toxoplasma and Plasmodium, respectively, to colonize and expand inside host cells. Therefore, deciphering how these two Apicomplexan protozoan parasites access their host cells has been highlighted as a priority research with the perspective of designing anti-invasive molecules to prevent diseases. Central to the mechanism of invasion for both genera is mechanical force, which is thought to be applied by the parasite at the interface between the two cells following assembly of a unique cell-cell junction but this model lacks direct evidence and has been challenged by recent genetic studies. In this work, using parasites expressing the fluorescent core component of this junction, we analyze characteristic features of the kinematics of penetration of more than 1,000 invasion events.

ResultsThe majority of invasion events occur with a typical forward rotational progression of the parasite through a static junction into an invaginating host cell plasma membrane. However, if parasites encounter resistance and if the junction is not strongly anchored to the host cell cortex, as when parasites do not secrete the toxofilin protein and, therefore, are unable to locally remodel the cortical actin cytoskeleton, the junction travels retrogradely with the host cell membrane along the parasite surface allowing the formation of a functional vacuole. Kinetic measurements of the invasive trajectories strongly support a similar parasite driven force in both static and capped junctions, both of which lead to successful invasion. However, about 20% of toxofilin mutants fail to enter and eventually disengage from the host cell membrane while the secreted RhOptry Neck RON2 molecules are posteriorally capped before being cleaved and released in the medium. By contrast in cells characterized by low cortex tension and high cortical actin dynamics junction capping and entry failure are drastically reduced.

ConclusionsThis kinematic analysis newly highlights that to invade cells parasites need to engage their motor with the junction molecular complex where force is efficiently applied only upon proper anchorage to the host cell membrane and cortex.

KeywordsCortical actin Host cell Invasion Kinematics Toxofilin Toxoplasma Electronic supplementary materialThe online version of this article doi:10.1186-s12915-014-0108-y contains supplementary material, which is available to authorized users.

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Autor: Marion Bichet - Candie Joly - Ahmed Hadj Henni - Thomas Guilbert - Marie Xémard - Vincent Tafani - Vanessa Lagal - Guillau

Fuente: https://link.springer.com/







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