title: ARF6 GTPase controls bacterial invasion by actin remodelling.
abstract: 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.
authors.affiliation: Unité de Biologie des Interactions Cellulaires, Institut Pasteur, CNRS URA 2582, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Balañá
authors.forename: Florence
authors.initials: F
authors.lastname: Niedergang
authors.forename: Agathe
authors.initials: A
authors.lastname: Subtil
authors.forename: Andrés
authors.initials: A
authors.lastname: Alcover
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavrier
authors.forename: Alice
authors.initials: A
authors.lastname: Dautry-Varsat
mesh_terms: 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
chemical_list: 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