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Arf GAP 1 restricts Mycobacterium tuberculosis entry by controlling the actin cytoskeleton
Author(s) -
Song OkRyul,
Queval Christophe J,
Iantomasi Raffaella,
Delorme Vincent,
Marion Sabrina,
VeyronChurlet Romain,
Werkmeister Elisabeth,
Popoff Michka,
Ricard Isabelle,
Jouny Samuel,
Deboosere Nathalie,
Lafont Frank,
Baulard Alain,
Yeramian Edouard,
Marsollier Laurent,
Hoffmann Eik,
Brodin Priscille
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744371
Subject(s) - mycobacterium tuberculosis , cytoskeleton , actin , microbiology and biotechnology , actin cytoskeleton , biology , chemistry , tuberculosis , genetics , cell , medicine , pathology
The interaction of Mycobacterium tuberculosis (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 ( PLD 1), and is dependent on the M3 muscarinic receptor (M 3 R). We show that this pathway is controlled by Arf GTP ase‐activating protein 1 (Arf GAP 1), 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 as Shigella flexneri and Yersinia pseudotuberculosis , 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 Arf GAP 1 as a restriction factor of host–pathogen interactions.