title: Toxoplasma gondii transmembrane microneme proteins and their modular design.
abstract: Host cell invasion by the Apicomplexa critically relies on regulated secretion of transmembrane micronemal proteins (TM-MICs). Toxoplasma gondii possesses functionally non-redundant MIC complexes that participate in gliding motility, host cell attachment, moving junction formation, rhoptry secretion and invasion. The TM-MICs are released onto the parasite's surface as complexes capable of interacting with host cell receptors. Additionally, TgMIC2 simultaneously connects to the actomyosin system via binding to aldolase. During invasion these adhesive complexes are shed from the surface notably via intramembrane cleavage of the TM-MICs by a rhomboid protease. Some TM-MICs act as escorters and assure trafficking of the complexes to the micronemes. We have investigated the properties of TgMIC6, TgMIC8, TgMIC8.2, TgAMA1 and the new micronemal protein TgMIC16 with respect to interaction with aldolase, susceptibility to rhomboid cleavage and presence of trafficking signals. We conclude that several TM-MICs lack targeting information within their C-terminal domains, indicating that trafficking depends on yet unidentified proteins interacting with their ectodomains. Most TM-MICs serve as substrates for a rhomboid protease and some of them are able to bind to aldolase. We also show that the residues responsible for binding to aldolase are essential for TgAMA1 but dispensable for TgMIC6 function during invasion.
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Lilach
authors.initials: L
authors.lastname: Sheiner
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Joana M
authors.initials: JM
authors.lastname: Santos
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Natacha
authors.initials: N
authors.lastname: Klages
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Parussini
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Noelle
authors.initials: N
authors.lastname: Jemmely
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Friedrich
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Ward
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Dominique
authors.initials: D
authors.lastname: Soldati-Favre
mesh_terms: D002448:Cell Adhesion; D004705:Endocytosis; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D021381:Protein Transport; D059748:Proteolysis; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000166:cytology / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D015800:Protozoan Proteins; D037521:Virulence Factors