title: Plasticity and redundancy among AMA-RON pairs ensure host cell entry of Toxoplasma parasites.
abstract: Malaria and toxoplasmosis are infectious diseases caused by the apicomplexan parasites Plasmodium and Toxoplasma gondii, respectively. These parasites have developed an invasion mechanism involving the formation of a moving junction (MJ) that anchors the parasite to the host cell and forms a ring through which the parasite penetrates. The composition and the assembly of the MJ, and in particular the presence of protein AMA1 and its interaction with protein RON2 at the MJ, have been the subject of intense controversy. Here, using reverse genetics, we show that AMA1, a vaccine candidate, interacts with RON2 to maintain the MJ structural integrity in T. gondii and is subsequently required for parasite internalization. Moreover, we show that disruption of the AMA1 gene results in upregulation of AMA1 and RON2 homologues that cooperate to support residual invasion. Our study highlights a considerable complexity and molecular plasticity in the architecture of the MJ.
authors.affiliation: UMR 5235 CNRS, Université de Montpellier 2, 34095 Montpellier, France.
authors.forename: Mauld H
authors.initials: MH
authors.lastname: Lamarque
authors.affiliation: UMR 5235 CNRS, Université de Montpellier 2, 34095 Montpellier, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Roques
authors.affiliation: UMR 5235 CNRS, Université de Montpellier 2, 34095 Montpellier, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Kong-Hap
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada V8W 3P6.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Tonkin
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 Rue Michel-Servet, 1211 Geneva 4, Switzerland.
authors.forename: George
authors.initials: G
authors.lastname: Rugarabamu
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 Rue Michel-Servet, 1211 Geneva 4, Switzerland.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Marq
authors.affiliation: UMR 5235 CNRS, Université de Montpellier 2, 34095 Montpellier, France.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Penarete-Vargas
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada V8W 3P6.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Boulanger
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 Rue Michel-Servet, 1211 Geneva 4, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Soldati-Favre
authors.affiliation: UMR 5235 CNRS, Université de Montpellier 2, 34095 Montpellier, France.
authors.forename: Maryse
authors.initials: M
authors.lastname: Lebrun
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014123:Toxoplasmosis / Q000469:parasitology*; D014774:Virulence
chemical_list: C506564:AMA1 protein, Toxoplasma gondii; D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C559757:rhoptry neck protein 2, Toxoplasma gondii