title: Caspase-11 and caspase-1 differentially modulate actin polymerization via RhoA and Slingshot proteins to promote bacterial clearance.
abstract: Inflammasomes are multiprotein complexes that include members of the NOD-like receptor family and caspase-1. Caspase-1 is required for the fusion of the Legionella vacuole with lysosomes. Caspase-11, independently of the inflammasome, also promotes phagolysosomal fusion. However, it is unclear how these proteases alter intracellular trafficking. Here, we show that caspase-11 and caspase-1 function in opposing manners to phosphorylate and dephosphorylate cofilin, respectively upon infection with Legionella. Caspase-11 targets cofilin via the RhoA GTPase, whereas caspase-1 engages the Slingshot phosphatase. The absence of either caspase-11 or caspase-1 maintains actin in the polymerized or depolymerized form, respectively and averts the fusion of pathogen-containing vacuoles with lysosomes. Therefore, caspase-11 and caspase-1 converge on the actin machinery with opposing effects to promote vesicular trafficking.
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus OH 43210.|Dorothy M. Davis Heart and Lung Research Institute, and The Ohio State University, Columbus OH 43210.
authors.forename: Kyle
authors.initials: K
authors.lastname: Caution
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, and The Ohio State University, Columbus OH 43210.
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Gavrilin
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus OH 43210.|Dorothy M. Davis Heart and Lung Research Institute, and The Ohio State University, Columbus OH 43210.
authors.forename: Mia
authors.initials: M
authors.lastname: Tazi
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus OH 43210.|Dorothy M. Davis Heart and Lung Research Institute, and The Ohio State University, Columbus OH 43210.
authors.forename: Apurva
authors.initials: A
authors.lastname: Kanneganti
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus OH 43210.|Dorothy M. Davis Heart and Lung Research Institute, and The Ohio State University, Columbus OH 43210.
authors.forename: Daniel
authors.initials: D
authors.lastname: Layman
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus OH 43210.|Dorothy M. Davis Heart and Lung Research Institute, and The Ohio State University, Columbus OH 43210.
authors.forename: Sheshadri
authors.initials: S
authors.lastname: Hoque
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus OH 43210.|Dorothy M. Davis Heart and Lung Research Institute, and The Ohio State University, Columbus OH 43210.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Krause
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus OH 43210.|Dorothy M. Davis Heart and Lung Research Institute, and The Ohio State University, Columbus OH 43210.
authors.forename: Amal O
authors.initials: AO
authors.lastname: Amer
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020170:Caspase 1 / Q000235:genetics* / Q000378:metabolism; D051338:Cofilin 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism; D016952:Legionella pneumophila / Q000235:genetics / Q000472:pathogenicity; D007877:Legionnaires' Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D051338:Cofilin 1; D058847:Inflammasomes; D046912:Multiprotein Complexes; D011956:Receptors, Cell Surface; D033921:Vesicular Transport Proteins; D010749:Phosphoprotein Phosphatases; C529575:SSH1 protein, mouse; D020170:Caspase 1; D020742:rhoA GTP-Binding Protein