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© Institut Pasteur
Cells infected for 24 hrs with C. Trachomatis. The cell nuclei are labelled in blue, the bacteria appear yellow, within the inclusion lumen. A bacterial protein secreted out the inclusion into the host cytoplasm id labelled in red.
Publication : EMBO reports

ArfGAP1 restrictsentry by controlling the actin cytoskeleton

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in EMBO reports - 28 Mar 2018

Song OR, Queval CJ, Iantomasi R, Delorme V, Marion S, Veyron-Churlet R, Werkmeister E, Popoff M, Ricard I, Jouny S, Deboosere N, Lafont F, Baulard A, Yeramian E, Marsollier L, Hoffmann E, Brodin P

Link to Pubmed [PMID] – 29141986

EMBO Rep. 2018 Jan;19(1):29-42

The interaction of(Mtb) with pulmonary epithelial cells is critical for early stages of bacillus colonization and during the progression of tuberculosis. Entry of Mtb into epithelial cells has been shown to depend on F-actin polymerization, though the molecular mechanisms are still unclear. Here, we demonstrate that mycobacterial uptake into epithelial cells requires rearrangements of the actin cytoskeleton, which are regulated by ADP-ribosylation factor 1 (Arf1) and phospholipase D1 (PLD1), and is dependent on the M3 muscarinic receptor (MR). We show that this pathway is controlled by Arf GTPase-activating protein 1 (ArfGAP1), as its silencing has an impact on actin cytoskeleton reorganization leading to uncontrolled uptake and replication of Mtb. Furthermore, we provide evidence that this pathway is critical for mycobacterial entry, while the cellular infection with other pathogens, such asand, is not affected. Altogether, these results reveal how cortical actin plays the role of a barrier to prevent mycobacterial entry into epithelial cells and indicate a novel role for ArfGAP1 as a restriction factor of host-pathogen interactions.

https://www.ncbi.nlm.nih.gov/pubmed/29141986