Toxoplasma gondii transmembrane microneme proteins and their modular design

• Published in: Molecular microbiology Vol. 77; no. 4; pp. 912 - 929
• Main Authors: Sheiner, Lilach, Santos, Joana M, Klages, Natacha, Parussini, Fabiola, Jemmely, Noelle, Friedrich, Nikolas, Ward, Gary E, Soldati-Favre, Dominique
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-08-2010; Blackwell Publishing Ltd; Blackwell
• Subjects: Apicomplexa; Biological and medical sciences; Cell Adhesion; Cells; Endocytosis; Fundamental and applied biological sciences. Psychology; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membranes; Microbiology; Parasitic protozoa; Protein Interaction Mapping; Protein Transport; Proteins; Proteolysis; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Toxoplasma - cytology; Toxoplasma - physiology; Toxoplasma gondii; Virulence Factors - genetics; Virulence Factors - metabolism; Transmembrane protein; Protozoa; Apicomplexa; Toxoplasma gondii
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/j.1365-2958.2010.07255.x

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.