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The toxoplasma-host cell junction is anchored to the cell cortex to sustain parasite invasive force

Overview of attention for article published in BMC Biology, December 2014
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Title
The toxoplasma-host cell junction is anchored to the cell cortex to sustain parasite invasive force
Published in
BMC Biology, December 2014
DOI 10.1186/s12915-014-0108-y
Pubmed ID
Authors

Marion Bichet, Candie Joly, Ahmed Hadj Henni, Thomas Guilbert, Marie Xémard, Vincent Tafani, Vanessa Lagal, Guillaume Charras, Isabelle Tardieux

Abstract

BackgroundThe public health threats imposed by toxoplasmosis worldwide and by malaria in sub-Saharan countries are directly associated with the capacity of their closely related causative agents Toxoplasma and Plasmodium, respectively to colonize and expand inside host cells. Therefore, deciphering how these two Apicomplexan protozoan parasites access their hosting cells has been highlighted as a high priority research with the relevant perspective of designing anti-invasive molecules to prevent diseases. Central to the mechanistic base 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 junction but this model lacks direct evidence and has been challenged by recent genetic and cell biology studies. In this work, using parasites expressing the fluorescent core component of this junction, we analyse characteristic features of the kinematics of penetration of more than 1000 invasion events.ResultsThe majority of invasion events occur with a typical forward rotational progression of the parasite through a static junction into a vacuole formed from the invaginating host cell plasma membrane, in which the parasite subsequently replicates. 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 is capped backwards and travels retrogradely with the host cell membrane along the parasite surface as it is enclosed within 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 RON2 molecules are capped at the posterior pole 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.ConclusionThis kinematic analysis of pre-invasive and invasive T. gondii tachyzoite behaviors 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.

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The data shown below were compiled from readership statistics for 65 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
India 1 2%
Unknown 63 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 19 29%
Researcher 10 15%
Student > Master 9 14%
Student > Bachelor 5 8%
Professor 4 6%
Other 8 12%
Unknown 10 15%
Readers by discipline Count As %
Agricultural and Biological Sciences 26 40%
Biochemistry, Genetics and Molecular Biology 9 14%
Medicine and Dentistry 7 11%
Veterinary Science and Veterinary Medicine 2 3%
Immunology and Microbiology 2 3%
Other 6 9%
Unknown 13 20%