title: The effect of kinase, actin, myosin and dynamin inhibitors on host cell egress by Toxoplasma gondii.
abstract: Toxoplasma gondii is a protozoan parasite that can infect the nucleated cells of all warm-blooded animals. Despite its medical and veterinary importance, the egress of T. gondii from host cells has not been fully elucidated. This process is usually studied with calcium ionophores, which artificially trigger T. gondii egress. Among the diverse signaling events that take place during egress, kinases appear to play a crucial role. In this work we employed several kinase inhibitors to examine their role in egress: although parasite egress was only slightly impaired by treatment with the PI3K and PKC inhibitors wortmannin and staurosporine, the addition of the tyrosine kinase-specific inhibitor genistein efficiently blocked the exit of parasites by more than 50%. IPA-3, a non-ATP-competitive inhibitor of p21-activated kinases, which play a role in actin cytoskeleton remodeling inhibited egress of T. gondii by only 15%. The myosin motor inhibitor blebbistatin and the actin polymerization inhibitor cytochalasin D also blocked the egress of T. gondii. Nevertheless, dynasore, which is known to block the GTPase activity of dynamin, had little or no effect on T. gondii egress.
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Lucio Ayres
authors.initials: LA
authors.lastname: Caldas
authors.forename: Sergio Henrique
authors.initials: SH
authors.lastname: Seabra
authors.forename: Márcia
authors.initials: M
authors.lastname: Attias
authors.forename: Wanderley
authors.initials: W
authors.lastname: de Souza
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology*; D034281:Dynamins / Q000037:antagonists & inhibitors; D004847:Epithelial Cells / Q000187:drug effects / Q000469:parasitology*; D019833:Genistein / Q000494:pharmacology*; D008253:Macaca mulatta; D051379:Mice; D009218:Myosins / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology*; D014122:Toxoplasma / Q000502:physiology*; D000077191:Wortmannin
chemical_list: D000199:Actins; D000730:Androstadienes; D047428:Protein Kinase Inhibitors; D015638:Cytochalasin D; D019833:Genistein; D009218:Myosins; D034281:Dynamins; D019311:Staurosporine; D000077191:Wortmannin
keywords: Actin; Apicomplexa; Calcium ionophore; Dynamin; Kinase; Myosin; Toxoplasma egress