ARF6 GTPase controls bacterial invasion by actin remodelling.
The obligate intracellular bacterium Chlamydia penetrates the host epithelial cell by inducing cytoskeleton and membrane rearrangements reminiscent of phagocytosis. Here we report that Chlamydia induces a sharp and transient activation of the endogenous small GTP-binding protein ARF6, which is required for efficient uptake. We also show that a downstream effector of ARF6, phosphatidylinositol 4-phosphate 5-kinase and its product, phosphatidylinositol 4,5-bisphosphate were instrumental for bacterial entry. By contrast, ARF6 activation of phospholipase D was not required for Chlamydia uptake. ARF6 activation was necessary for extensive actin reorganization at the invasion sites. Remarkably, these signalling players gathered with F-actin in a highly organized three-dimensional concentric calyx-like protrusion around invasive bacteria. These results indicate that ARF6, which controls membrane delivery during phagocytosis of red blood cells in macrophages, has a different role in the entry of this small bacterium, controlling cytoskeletal reorganization.
Balañá
María Eugenia
ME
Unité de Biologie des Interactions Cellulaires, Institut Pasteur, CNRS URA 2582, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Niedergang
Florence
F
Subtil
Agathe
A
Alcover
Andrés
A
Chavrier
Philippe
P
Dautry-Varsat
Alice
A
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000502:physiology*; D000199:Actins / Q000378:metabolism*; D002689:Chlamydia / Q000502:physiology*; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism
D000089982:ADP-Ribosylation Factor 6; D000199:Actins; D019269:Phosphatidylinositol 4,5-Diphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D010739:Phospholipase D; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human