title: Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion.
abstract: Apicomplexan parasites secrete transmembrane (TM) adhesive proteins as part of the process leading to host cell attachment and invasion. These microneme proteins are cleaved in their TM domains by an unidentified protease termed microneme protein protease 1 (MPP1). The cleavage site sequence (IA downward arrowGG), mapped in the Toxoplasma gondii microneme proteins TgMIC2 and TgMIC6, is conserved in microneme proteins of other apicomplexans including Plasmodium species. We report here the characterisation of novel T. gondii proteins belonging to the rhomboid family of intramembrane-cleaving serine proteases. T. gondii possesses six genes encoding rhomboid-like proteins. Four are localised along the secretory pathway and therefore constitute possible candidates for MPP1 activity. Toxoplasma rhomboids TgROM1, TgROM2 and TgROM5 cleave the TM domain of Drosophila Spitz, an established substrate for rhomboids from several species, demonstrating that they are active proteases. In addition, TgROM2 cleaves chimeric proteins that contain the TM domains of TgMIC2 and TgMIC12.
authors.affiliation: Department of Biological Sciences, Imperial College London, Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Dowse
authors.forename: John C
authors.initials: JC
authors.lastname: Pascall
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Brown
authors.forename: Dominique
authors.initials: D
authors.lastname: Soldati
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004789:Enzyme Activation; D019084:Fluorescent Antibody Technique, Indirect; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D014122:Toxoplasma / Q000378:metabolism*; D014123:Toxoplasmosis / Q000378:metabolism* / Q000635:transmission
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C105877:MIC1 protein, Toxoplasma gondii; C408878:MIC2 protein, Toxoplasma gondii; D008565:Membrane Proteins; D015800:Protozoan Proteins; C081481:Rho protein, Drosophila; D012697:Serine Endopeptidases